JP3194748B2 - Pyrazole derivatives - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a novel pyrazole derivative, a herbicide containing the pyrazole derivative as an active ingredient, and an intermediate suitable for producing the pyrazole derivative.

Background Art and Problems to be Solved by the Invention Herbicides are extremely important agents for labor saving of weed control work and improvement of productivity of agricultural and horticultural crops. Therefore, research and development of herbicides has been actively carried out for many years. Currently, a wide variety of drugs are in practical use. However, even today, there is a demand for the development of a novel drug having more excellent herbicidal properties, particularly a drug capable of controlling only the target weed selectively and at a low dose without damaging the cultivated crop.

Conventionally, at the time of cultivation of corn and the like, atrazine which is a triazine herbicide and arachlor and metolachlor which are acid anilide herbicides have been used. Crawl, on the other hand, has low activity against broadleaf weeds. Therefore, it is currently difficult to control grasses and broadleaf weeds at once with a single agent.
Furthermore, these herbicides require high dosages and are not preferred on environmental issues.

In addition, in the paddy field, together with rice, various weeds, such as annual grasses such as Nobie, annual cyperaceae weeds such as stag beetle, annual broadleaf weeds such as scallops and kakashigusa, urikawa, hirumushiro, haramodaka, fireflies, pine trees, squirrels, It is known that perennial weeds such as Krogwai, Omodaka and Seri grow, and it is necessary to spray these weeds efficiently with a small amount of spraying without damaging the rice and environmental pollution. Is extremely important to It is generally known that chemicals having high herbicidal activity against Nobies are likely to cause harm to rice, but they show high herbicidal activity against Nobies, a grass weed, and selectivity between genus and rice. The development of highly effective drugs has become a particularly important issue.

Incidentally, it is known that a specific 4-benzoylpyrazole derivative has herbicidal activity (JP-A-63-1226).
No. 72, 63-1222673, 63-170365, JP-A-1-52
No. 759, No. 2-173, No. 2-288866), and a commercially available herbicide includes a pyrazolate represented by the following chemical formula.

The chemical formula of (A) (compound No. 35 in JP-A-2-173), which is a typical example of the 4-benzoylpyrazole derivative described in the above publication, is shown below.

Compound (A): Compound No. 35 described in JP-A-2-173 However, although these 4-benzoylpyrazole derivatives have herbicidal activity, they are practically insufficient, and in particular, their herbicidal activities on grass weeds such as Nobie and Enokorogosa are extremely poor. In addition, when used as a paddy herbicide, poor selectivity between paddy rice and grass weeds may cause harm to paddy rice.

Therefore, the present inventors have proposed a pyrazole derivative having a thiochroman ring, and have already filed a patent application (Japanese Patent Application No. 4-185526 and International Publication WO93 / 18031). Representative examples (B) and (C) of the compounds described in the specifications of these prior applications are shown below.

Compound (B): a compound described in International Publication WO93 / 18031
No.66 Compound (C): Compound N described in Japanese Patent Application No. 4-185526.
ob-3 However, these compounds have high herbicidal activity, but leave room for improvement in terms of safety against rice.

The present invention has been made in view of the above circumstances,
Its purpose is to have no harm to crops such as corn and rice, and to have a wide range of upland weeds and paddy weeds.
In particular, it is an object of the present invention to provide a pyrazole derivative capable of controlling nobies at low doses in paddy fields, a herbicide using the same, and an intermediate for obtaining the pyrazole derivative.

DISCLOSURE OF THE INVENTION The present invention provides a compound of formula (I) Wherein R ¹ is a hydrogen atom or a C ₁ -C ₄ alkyl group; R ² is a C ₁ -C ₄ alkyl group; X ¹ is a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group X ² , X ³ , X ⁵ , X ⁶ , X ⁷ and X ⁸ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group, or X ² And X ⁵ or X ⁵ and X ⁷ can be bonded to each other to form an unsaturated bond; X ⁴ is one selected from the group consisting of a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group ; Q is the radical [formula represented by hydrogen or the formula -A-B, a is -SO ₂ - is one selected from the group consisting of group, -CO- group and -CH ₂ CO- group, B is a C ₁ -C ₈ alkyl group, a C ₃ -C ₈ cycloalkyl group and a compound of the formula (V) Wherein Y is one selected from the group consisting of a halogen atom, a nitro group, a C ₁ -C ₄ alkyl group, a C ₁ -C ₄ alkoxy group and a C ₁ -C ₄ haloalkyl group; 1 or 2
Represents an integer. ) Is selected from the group consisting of:
N is 0, 1 or 2; p represents 0 or 1

However, when X ² and X ³ are simultaneously a C ₁ -C ₄ alkyl group and p is 1, the case where X ⁵ , X ⁶ , X ⁷ and X ⁸ are simultaneously a hydrogen atom is excluded. The first aspect is a pyrazole derivative represented by｝ or a salt thereof.

The second aspect of the present invention provides a herbicide comprising a pyrazole derivative represented by the above formula (I) and / or a salt thereof as an active ingredient.

Further, the present invention provides a compound of the formula (II) useful for producing the pyrazole derivative represented by the above formula (I). Wherein X ¹ is a halogen atom or a C ₁ -C ₄ alkyl group; X ² , X ³ , X ⁵ , X ⁶ , X ⁷ and X ⁸ are each independently a hydrogen atom or a C ₁ -C 4 X _{4 is} an alkyl group or X ² and X ⁵ or X ⁵ and X ⁷ can be bonded to each other to form an unsaturated bond; X ⁴ is a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group N is 0, 1 or 2; and p represents 0 or 1.

However, when X ² and X ³ are simultaneously a C ₁ -C ₄ alkyl group and p is 1, the case where X ⁵ , X ⁶ , X ⁷ and X ⁸ are simultaneously a hydrogen atom is excluded. An aromatic carboxylic acid derivative represented by｝ or a salt thereof is a third aspect.

BEST MODE FOR CARRYING OUT THE INVENTION The novel pyrazole derivative of the present invention has the formula (I) It is a compound represented by these.

In formula (I), R ¹ is a hydrogen atom or a C ₁ -C ₄ alkyl group, preferably a hydrogen atom. R ² is C ₁ -C ₄ alkyl group. Here, the C ₁ -C ₄ alkyl group as R ¹ and R ² includes, for example, a methyl group, an ethyl group, a n-propyl group, a propyl group such as an i-propyl group, an n-butyl group,
and butyl groups such as i-butyl group. As R ²
The C ₁ -C ₄ alkyl group, an ethyl group are preferable.

X ¹ is one selected from the group consisting of a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group. Examples of the halogen atom as X ¹ include fluorine, chlorine, bromine and iodine, and examples of the C ₁ -C ₄ alkyl group include those exemplified for R ¹ and R ² . Preferably C ₁ -C ₄ alkyl group,
More preferably, it is a methyl group.

X ² , X ³ , X ⁵ , X ⁶ , X ⁷ and X ⁸ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group, or X ²
Can also be X ⁵ or X ⁵ and X ⁷ are combined to form a unsaturated bond with each other. As the C ₁ -C ₄ alkyl group, R ¹ and R ²
And the like. Preferably, each is independently a hydrogen atom, a methyl group or an ethyl group, or the case where X ² and X ⁵ are bonded to each other to form a double bond.

X ⁴ is one selected from the group consisting of a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group. The halogen atom is exemplified in X ^1, as the C ₁ -C ₄ alkyl group include those exemplified for R ¹ and R ^2. Preferably a hydrogen atom, C ₁ -C ₄ alkyl group, more preferably a methyl group. Further, when the substitution position of X ⁴ is p = 0, preferably the 7-position of the benzo [b] thiophene ring, and when p = 1,
Preferred is position 8 of the thiochroman ring.

Q is a hydrogen atom or a group represented by the formula -AB,
A is -SO ₂ - group, represents one selected from the group consisting of -CO- group and -CH ₂ CO- group, B is C ₁ -C ₈ alkyl group, C ₃ ~
C ₈ cycloalkyl group and formula (V) Is one selected from the group consisting of groups represented by

Here, the C ₁ -C ₈ alkyl group which is one embodiment of B includes, for example, a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, and the like. In the case of three or more, it may be linear or branched. Preferably, it is an ethyl group, an n-propyl group or an i-propyl group. Examples of the C ₃ -C ₈ cycloalkyl group which is another embodiment of B include, for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, and the like. is there.

Furthermore, in the group of the formula (V) which is another embodiment of B, Y
Halogen atom, nitro group, C ₁ -C ₄ alkyl groups, C ₁ -C ₄
An alkoxy group or a C ₁ -C ₄ haloalkyl group. Examples of the halogen atom include those exemplified by X ¹ and X ^4, as the C ₁ -C ₄ alkyl group include those exemplified for R ¹ and R ^2, preferably a methyl group. C ₁
The -C ₄ alkoxy, such as methoxy group, an ethoxy group, an propoxy be branched, butoxy group. C ₁ The -C ₄ haloalkyl groups, e.g., those replaced by exemplified halogen atom hydrogen atom of C ₁ -C ₄ alkyl groups exemplified for R ¹ and R ² in X ¹ and X ^4,
_{Specifically, -CH 2 F, -CHF 2,} -CF 3, -CF 2 CF 3, -CCl
₃ , —CH ₂ CF _{3 and the} like.

 M indicating the number of Y is an integer of 0, 1 or 2.

As an embodiment of the combination of A and B of the preferred -A-B group, for example, A is -SO ₂ - when group, B is C ₁ -C ₈ alkyl group or one or two halogen atoms, a nitro group,
A phenyl group substituted with a C ₁ -C ₄ alkyl group or a C ₁ -C ₄ alkoxy group (in the formula (V), Y is a halogen atom, a nitro group, a C ₁ -C ₄ alkyl group or a C ₁ -C ₄ alkoxy group) And m is 1 or 2. Other aspects of the preferred combination of A and B, when A is -CO- group or -CH ₂ CO- group, B is C ₁ -C ₈ alkyl group or a halogen-substituted or unsubstituted phenyl group (the formula (V )), Wherein Y is a halogen atom and m is 0, 1 or 2.

n represents the number of oxygen and is an integer of 0, 1, or 2, respectively. That is, when n is 0, it indicates a sulfide, when n is 1, it indicates a sulfoxide, and when n is 2, it indicates a sulfone.

p is an integer of 0 or 1, and when p is 1, the pyrazole derivative of the general formula (I) is represented by the general formula (I x) And when p is 0, the pyrazole derivative of the general formula (I) is represented by the general formula (Iy) Represents a pyrazole derivative represented by

A pyrazole derivative of the general formula (I) wherein Q is hydrogen, ie Has the following three types of structures due to tautomerism, and the pyrazole derivative of the present invention includes all of these structures.

Further, the pyrazole derivative represented by the formula (Ia) is an acidic substance, and can be easily converted into a salt by treating with a base, and this salt is also included in the pyrazole derivative of the present invention. Here, the base is not particularly limited as long as it is known, and examples thereof include organic bases such as amines and anilines, and inorganic bases such as sodium compounds and potassium compounds. Examples of the amines include monoalkylamine, dialkylamine, and trialkylamine. Alkyl groups in alkylamines are usually C ₁ to
C ₄ alkyl group. Anilines include aniline, monoalkylaniline, dialkylaniline and the like. Alkyl group in the alkyl anilines is usually C ₁ -C ₄ alkyl group. Examples of the sodium compound include sodium hydroxide and sodium carbonate, and examples of the potassium compound include potassium hydroxide and potassium carbonate.

The herbicide of the present invention contains, as an active ingredient, the novel pyrazole derivative of the present invention represented by the formula (I) and / or a salt thereof, and converts these compounds into a liquid carrier such as a solvent or a mineral fine powder. Mixed with a solid carrier such as
It can be formulated and used in the form of wettable powders, emulsions, powders, granules and the like. A surfactant may be added to impart emulsifiability, dispersibility, spreadability, and the like during formulation.

When the herbicide of the present invention is used in the form of a wettable powder, the pyrazole derivative of the present invention and / or a salt thereof is usually 10 to 55.
The composition may be prepared by blending at a ratio of 40% to 88% by weight of a solid carrier and 2 to 5% by weight of a surfactant and used. When used in the form of an emulsion, usually, the pyrazole derivative of the present invention and / or a salt thereof 20 to 50% by weight,
What is necessary is just to mix and prepare in the ratio of 35-75 weight% of a solvent and 5-15 weight% of surfactant.

On the other hand, when used in the form of a powder, it is usually prepared by blending the pyrazole derivative of the present invention and / or a salt thereof in a proportion of 1 to 15% by weight, a solid carrier in an amount of 80 to 97% by weight and a surfactant in a proportion of 2 to 5% by weight. do it. Further, when used in the form of granules, the pyrazole derivative of the present invention and / or a salt thereof is prepared in a proportion of 1 to 15% by weight, a solid carrier in a proportion of 80 to 97% by weight, and a surfactant in a proportion of 2 to 5% by weight. do it.

Here, fine powder of a mineral substance is used as the solid carrier. Examples of the fine powder of the mineral substance include oxides such as diatomaceous earth, slaked lime, phosphates such as apatite, sulfates such as gypsum, talc, and pyrolite. Ferrite, clay, kaolin, bentonite, acid clay, white carbon, quartz powder, silicate such as silica stone powder, and the like can be given.

As the solvent, an organic solvent is used, and specifically, aromatic hydrocarbons such as benzene, toluene, and xylene, o
Chlorinated hydrocarbons such as chlorotoluene, trichloroethane, trichloroethylene, alcohols such as cyclohexanol, amyl alcohol, ethylene glycol,
Ketones such as isophorone, cyclohexanone, cyclohexenyl-cyclohexanone, butyl cellosolve, diethyl ether, ethers such as methyl ethyl ether,
Esters such as isopropyl acetate, benzyl acetate, and methyl phthalate; amides such as dimethylformamide; and mixtures thereof.

Furthermore, as the surfactant, any of an anionic type, a nonionic type, a cationic type and a zwitterionic type (amino acid, betaine, etc.) can be used.

The herbicide of the present invention may contain, if necessary, other herbicidal active ingredients together with the pyrazole derivative represented by the above general formula (I) and / or a salt thereof as an active ingredient. As such other herbicidal active ingredients,
Conventionally known herbicides, for example, phenoxy, diphenyl ether, triazine, urea, carbamate, thiocarbamate, acid anilide, pyrazole, phosphoric acid, sulfonylurea, oxadiazon, etc. And herbicides can be appropriately selected and used.

Furthermore, the herbicide of the present invention can be mixed with an insecticide, a fungicide, a plant growth regulator, a fertilizer, and the like, if necessary.

The novel pyrazole derivative represented by the formula (I) of the present invention is produced by the following methods (1) and (2).

First, the method (1) for producing a pyrazole derivative of the present invention will be described in detail.

In the above reaction formula, Q ¹ is a group represented by the formula -AB, and A is one selected from the group consisting of a -SO ₂ -group, a -CO- group and a -CH ₂ CO- group. B represents a C ₁ -C ₈ alkyl group,
C ₃ -C ₈ cycloalkyl group and the formula (V) Wherein Y is a halogen atom, a nitro group, C ₁
-C ₄ alkyl group, C ₁ -C ₄ alkoxy group and halo C ₁ -C ₄
Is one selected from the group consisting of alkyl groups, and m is Y
And represents an integer of 0, 1 or 2). R ¹ , R ² , X ¹ , X ² , X ³ ,
X ⁴ , X ⁵ , X ⁶ , X ⁷ , X ⁸ , p and n represent the same as defined above in formula (I), and Hal represents a halogen atom.

 Hereinafter, the manufacturing method will be described in detail for each step.

(Step 1) A compound of the formula (II) and a compound of the formula (III) are dehydrated,
For example, DCC (N, N'-dicyclohexylcarbodiimide), CDI (1,1-carbonyldiimidazole), EDC
The reaction is carried out in an inert solvent in the presence of (1- (3-dimethylaminopropyl) -3-ethylcarbodiimide) or the like and a base to produce a pyrazole derivative (Ia).

The compound of the formula (III) is added to the compound of the formula (II) by 1.0
It is preferably used in a molar amount of up to 3.0 times. The dehydrating agent is preferably used in an amount of 1.0 to 1.5 times the molar amount of the compound of the formula (II). The type of the base is not particularly limited, but is preferably potassium carbonate, sodium carbonate, or the like, and is preferably used in an amount of 0.5 to 2.0 times the molar amount of the compound of the formula (II). The reaction solvent is not particularly limited as long as it is inert to the reaction,
Acetonitrile, 1,4-dioxane, t-amyl alcohol, t-butyl alcohol, i-propyl alcohol and the like are preferred. The reaction temperature can be selected from the range of 0 ° C. to the boiling point of the solvent, but is preferably about 80 ° C. The reaction time is 1 to 48 hours, usually about 8 hours.

In addition, an ester is produced as a reaction intermediate, and this ester intermediate can be isolated by means such as silica gel column chromatography, but usually the reaction proceeds without isolation. When the ester intermediate is isolated, the target pyrazole derivative (Ia) can be obtained by adding a base such as potassium carbonate and further reacting the ester intermediate. The amount of the base used in this case is 0.5 to 3.0 equivalents, preferably 0.5 to 1.5 equivalents, based on the ester intermediate.
The reaction temperature is generally 80-150 ° C., preferably 100-150 ° C.
~ 120 ° C. The reaction time is generally 0.5 to 8 hours, preferably about 1 to 2 hours.

After completion of the reaction, according to a conventional method, after distilling off the solvent, liquid separation was performed with an organic solvent and water, and the obtained aqueous layer was neutralized with an acid such as hydrochloric acid,
The target pyrazole derivative (Ia) can be isolated by extracting with ethyl acetate, drying the organic layer with a dehydrating agent such as anhydrous sodium sulfate, and distilling off the solvent.

(Step 2) Compound (Ia) obtained in Step 1 was subjected to Q ^{1 in} the presence of a base.
-Hal (IV) (Q ¹ and Hal represents a as defined above)
And in an inert solvent to produce compound (Id).

In this step, the molar ratio of the compound (Ia) to the compound (IV) is preferably 1: 1 to 1: 3. In order to capture hydrogen halide by-produced by the reaction, sodium carbonate and potassium carbonate are used. It is preferred to use a base such as triethylamine, pyridine or the like in a molar ratio or more with respect to the starting material of the formula (Ia). The reaction temperature is preferably in the range from room temperature to the boiling point of the solvent used. Examples of the solvent used in the reaction include aromatic hydrocarbons such as benzene and toluene, ethers such as diethyl ether, ketones such as methyl ethyl ketone, and halogenated hydrocarbons such as methylene chloride and chloroform. A two-phase solvent composed of these solvents and water can also be used. In this case, a favorable result can be obtained by adding a phase transfer catalyst such as crown ether or benzyltriethylammonium chloride to the reaction system.

After the completion of the reaction, liquid separation is performed according to a conventional method, the target substance is extracted from the aqueous layer with an organic solvent such as dichloromethane, the organic layer is dehydrated, and then the solvent is distilled off to obtain the target pyrazole derivative (Id). Can be isolated.

Formula (II) used for the reaction with the compound of Formula (III) in the above method Wherein X ¹ is a hydrogen atom, a halogen atom or a C ₁ -C ₄ alkyl group; X ² , X ³ , X ⁵ , X ⁶ , X ⁷ and X ⁸ are each independently a hydrogen atom or C X _{1 is a} C ₄ alkyl group, or X ² and X ⁵ or X ⁵ and X ⁷ can be bonded to each other to form an unsaturated bond; X ⁴ is a hydrogen atom, a halogen atom or C ₁ -C _{4 is} an alkyl group; n is 0, 1 or 2; p represents 0 or 1;

However, when X ² and X ³ are simultaneously a C ₁ -C ₄ alkyl group and p is 1, the case where X ⁵ , X ⁶ , X ⁷ and X ⁸ are simultaneously a hydrogen atom is excluded. The aromatic carboxylic acid derivative represented by｝ is a novel compound not described in any literature, and is useful as an intermediate for producing the pyrazole derivative of the present invention.

Specific examples of X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ and X ^{8 in} the formula (II) include those exemplified for the pyrazole derivative of the formula (I).

The aromatic carboxylic acid derivative represented by the formula (II) is an acidic substance, and can be easily converted into a salt by treating with a base. This salt is also included in the aromatic carboxylic acid derivative of the present invention. is there. Here, the base is not particularly limited as long as it is known, and examples thereof include organic bases such as amines and anilines and inorganic bases such as sodium compounds and potassium compounds. Examples of amines include monoalkylamine, dialkylamine, and trialkylamine. Alkyl group in the alkyl amines are generally C ₁ -C ₄ alkyl group. Examples of anilines include aniline, monoalkylaniline, dialkylaniline and the like. As the alkyl group in the alkyl anilines is usually C ₁ -C ₄ alkyl group. Examples of the sodium compound include sodium hydroxide and sodium carbonate, and examples of the potassium compound include potassium hydroxide and potassium carbonate.

Compounds in which p is 1 among the aromatic carboxylic acid derivatives represented by the general formula (II) (however, X ² and X ⁵ and ⁵ and X ⁷ are not bonded to each other), that is, the general formula (II x) The aromatic carboxylic acid derivative represented by is produced by the methods represented by the following production schemes 1 to 6.

In the above reaction formula, X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ , X ⁸
And Hal are as defined above.

The thiophenols of the formula (VI) as starting materials can be obtained by known methods (for example, see "New Experimental Chemistry 14,
Synthesis and Reaction of Organic Compounds III, page 1704 Chapter 8.1 Thiols f. Synthetic Method via Dithiocarbonate, Maruzen Co., Ltd., issued February 20, 1986).

(Step 1) A starting material of the formula (VI) and a compound of the formula (VII) are mixed in an inert solvent such as acetone, diethyl ether or dimethylformamide in anhydrous potassium carbonate, sodium hydroxide, potassium hydroxide, anhydrous sodium carbonate, Reaction in the presence of a base such as triethylamine gives the compound of formula (VIII). The compound of formula (VIII) and the base are used in amounts of 1.0 to 1.5 and 1.0 to 1.5 molar equivalents, respectively, relative to the starting material of formula (VI). The reaction temperature is preferably from 0 to 80 ° C, and the reaction time is preferably from about 1 to 8 hours.

(Step 2) A compound of formula (VIII) (thiochroman compound) is obtained by adding a dehydrating condensing agent such as polyphosphoric acid, sulfuric acid, phosphorus pentoxide and the like to the compound of formula (VIII) to effect ring closure. The dehydrating condensing agent has the formula (VI
It is used in an amount of 1 to 10 molar equivalents relative to the compound of II). The reaction temperature is preferably from 0 to 100 ° C., and the reaction time is preferably from about 1 to 8 hours.

(Step 3) A compound of the formula (IX) is added to methylene chloride, chloroform,
In the presence of a solvent such as carbon tetrachloride, bromine, sulfuryl chloride,
A halogenating reagent such as chlorine is reacted to obtain a compound of the formula (X) substituted with a halogen at the 6-position. The reaction temperature is usually 0
The reaction time is preferably about 1 to 80 hours.

(Step 4) The compound of the formula (X) is reacted with magnesium (Mg) to obtain a Grignard reagent, which is reacted with carbon dioxide (CO ₂ ) to obtain a compound of the formula (II) of the present invention having a carboxyl group introduced at the 6-position. Compound (XI) which is an aromatic carboxylic acid derivative of x)
(N = 0, sulfide compound) is obtained. It is preferable to use ethers such as diethyl ether and tetrahydrofuran as the solvent. The reaction temperature is 0-70 ° C, especially 20-
60 ° C. is preferred. The reaction time is usually about 1 to 7 hours.

The amount of magnesium (Mg) for obtaining the Grignard reagent is preferably 1.1 to 3.5 molar equivalents relative to the compound of the formula (X). The Grignard reaction is preferably performed in the presence of an alkyl iodide such as methyl iodide or an alkyl bromide such as ethyl bromide, since the reaction proceeds smoothly. The amount of the alkyl halide used at this time is preferably 0.1 to 2.5 molar equivalents relative to the compound of the formula (X).

The reaction between Grignard reagent and carbon dioxide (CO ₂ ) can be performed by blowing carbon dioxide gas from a cylinder into the Grignard reagent in the solvent or dry ice (solid carbon dioxide).
This is performed by blowing in carbon dioxide gas generated from. Alternatively, dry ice may be added directly to the Grignard reagent for reaction.

(Step 5) An oxidizing agent (eg, hydrogen peroxide, peracetic acid, sodium metaperiodate, etc.) is added to a compound of the formula (XI) (in the formula (IIx), n = 0, a sulfide compound) with a solvent (eg, acetic acid, (Water, methanol, etc.)
Compound (XII) which is an aromatic carboxylic acid derivative of x)
(N = 1, sulfoxide compound / n = 2, sulfone compound) is obtained. By reacting one equivalent of an oxidizing agent with respect to compound (XI), sulfoxide (compound of n = 1) is obtained.
By reacting two equivalents, a sulfone (a compound with n = 2) is obtained.

(Steps 1 and 2) Compound (I) from starting material (VI) via compound (VIII)
Steps 1 and 2 for producing X) are the same as those for producing compound (IX) from compound (VI) in Scheme 1.

(Step 3) A compound of the formula (IX) is added to dichloromethane, nitromethane,
In the presence of a solvent such as acetonitrile and benzene, acetyl chloride was reacted with a Lewis acid such as aluminum chloride, zinc chloride and iron chloride or a proton acid such as hydrogen fluoride, sulfuric acid and phosphoric acid to introduce an acetyl group at the 6-position. Compound (XII
I get. The Lewis acid and the protonic acid are used in an amount of 1.0 to 1.5 molar equivalents, and the acetyl chloride is used in an amount of 1.0 to 1.5 molar equivalents based on the compound (IX). The reaction temperature is usually 0 to 80 ° C, and the reaction time is 1 to
About 8 hours are preferable.

(Step 4) Compound (XIV) is obtained by reacting compound (XIII) (sulfide) with an oxidizing agent (eg, hydrogen peroxide, peracetic acid, sodium metaperiodate, etc.) in a solvent (eg, acetic acid, water, methanol, etc.). (N = 1, sulfoxide compound / n = 2, sulfone compound) is obtained. The compound (XIII) is reacted with one equivalent of an oxidizing agent to give a sulfoxide compound (n =
By reacting two equivalents of the compound (1), a sulfone compound (n = 2) can be obtained.

(Step 4 ′) A method for converting a methyl ketone group (acetyl group) at the 6-position into a carboxyl group without oxidizing the sulfur atom S of the thiochroman ring is described in J. Am. Chem. Soc. 66 , p. 1612 (1944). There is a method described. That is, the methyl ketone compound of the formula (XIII) is reacted with iodine in pyridine and decomposed with an alkali to give the compound (XI) (n = 0, a sulfide compound) which is an aromatic carboxylic acid derivative of the formula (II x) of the present invention. ) Is obtained.

(Step 5) The methyl ketone compound (XIV) is an aromatic carboxylic acid derivative (IIx) of the present invention by a haloform reaction using an oxidizing agent (eg, permanganate, chromate, halogen, oxygen, sulfuric acid, etc.). Conversion to compound (XII) (n = 1, sulfoxide compound / n = 2, sulfone compound).

The aromatic carboxylic acid derivative represented by the general formula (IIx) can be generally produced by a method represented by the following production scheme 3.

(Step 1) A thiophenol represented by the formula (VI) and an alcohol represented by the formula (XV) are converted into an aromatic solvent such as benzene or toluene, or a halogenated hydrocarbon solvent such as dichloroethane or tetrachloroethane. Medium, an acid catalyst such as sulfuric acid, p-toluenesulfonic acid, methanesulfonic acid, formic acid, and acetic acid is added and reacted to produce a compound represented by the formula (XVI). The alcohol of the formula (XV) is used in an amount of 1.0 to 3.0 mole equivalent to the thiophenol of the formula (VI). The acid catalyst is used in an amount of 0.01 to 1.0 molar equivalent to thiophenols.
Acetic acid, formic acid, etc. may be used also as a solvent. The reaction temperature can be from room temperature to the boiling point of the solvent.
0 ° C.

(Step 2) reacting the compound of formula (XVI) with a Grignard reagent,
Producing alcohols of formula (XVII). This step is a well-known Grignard reaction, and the details are omitted.

(Step 3) An alcohol of the formula (XVII) is reacted with a dehydrating agent such as polyphosphoric acid, diphosphorus pentoxide, sulfuric acid or the like, or is reacted with an acid catalyst such as methanesulfonic acid or p-toluenesulfonic acid. This is a step of producing a compound of the formula (XIX).
As a solvent, aromatic hydrocarbons such as benzene and toluene,
Alternatively, a halogenated hydrocarbon solvent such as dichloroethane and tetrachloroethane can be used. In the case of polyphosphoric acid or sulfuric acid, it can be used as a solvent. The reaction temperature can be from room temperature to the boiling point of the solvent.
C. to 100C.

(Step 4) The alcohols of the formula (XVII) include, for example, thionyl chloride,
In this step, a halogenating agent such as phosphorus oxychloride or phosphorus pentachloride is reacted to obtain a halogen compound of the formula (XVIII). The halogenating agent is used for the alcohol of the formula (XVII)
Use 1.0 to 1.5 molar equivalents. The solvent is not particularly limited as long as it is inert to the reaction, and examples thereof include those exemplified in Step 3. Thionyl chloride or phosphorus oxychloride which is a halogenating agent may be used as a solvent. The reaction temperature can be from room temperature to the boiling point, but is usually from 60 ° C to 80 ° C.

(Step 5) Aluminum chloride is added to the halogen compound of the formula (XVIII),
A Lewis acid such as zinc chloride or iron chloride is allowed to act, and the formula (XI
This is a step of producing the compound of X). Aluminum chloride is preferred. The Lewis acid is 1.0 to the compound of formula (XIX)
Use up to 1.5 molar equivalents. As the solvent, methylene chloride,
Halogenated hydrocarbon solvents such as dichloroethane are preferred. The reaction temperature can be from 0 ° C. to the boiling point of the solvent, but usually the reaction proceeds smoothly at around room temperature.

The compound of the formula (XIX) is produced by the above steps, and the following reaction is carried out in the same manner as in the above production scheme 1 or 2, to obtain an aromatic carboxylic acid of the general formula (IIx).

(Step 1) A brominated thiochroman-4-one compound (XX) as a starting material is prepared by a known method, for example, JP-A-58-198483,
It can be produced by the method described in International Publication WO88 / 06155 and the like. A Grignard reagent is reacted with a brominated thiochroman-4-one compound represented by the formula (XX) to obtain a thiochromanol derivative represented by the formula (XXI). This step is a typical Grignard reaction, and details are omitted.

(Step 2) In a step of dehydrating a thiochromanol derivative represented by the formula (XXI) using an acid catalyst in an organic solvent to give a 3,4-dehydrothiochroman derivative represented by the formula (XXII) is there. Examples of the acid catalyst used include sulfuric acid, p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid and the like. The acid catalyst is a thiochromanol derivative (XX
0.001 to 1.0 molar equivalent to I), preferably 0.01 to 0.1
Use molar equivalents. Benzene,
Examples include aromatic hydrocarbon solvents such as toluene, and halogenated hydrocarbon solvents such as 1,2-dichloroethane, 1,1,1-trichloroethane, and carbon tetrachloride. The reaction temperature is generally from 60 to 120C, preferably from 80 to 100C.

(Step 3) In this step, the 3,4-dehydrothiochroman derivative represented by the formula (XXII) is reduced to a thiochroman derivative of the formula (XXIII). The method of reduction is not particularly limited, but a method of reducing with hydrogen at normal pressure or under pressure in the presence of a catalyst such as palladium or platinum is preferable.

Thereafter, carboxylation and oxidation are carried out in the same manner as in the above Production Scheme 1 to obtain an aromatic carboxylic acid of the general formula (IIx).

(Step 1) A thiophenol represented by the formula (VI) and a thiophenol represented by the formula (XXIV)
Wherein α, β-unsaturated ketones represented by the formula are reacted in the presence of a basic catalyst such as pyridine, piperidine or triethylamine to give sulfides of the formula (XVIa), Is not particularly limited as long as it is inert to the reaction, for example, halogenated hydrocarbons such as 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2,2-tetrachloroethane Solvents are preferred. The reaction temperature can be from room temperature to the boiling point of the solvent, but generally the reaction proceeds smoothly around room temperature. Formula (XX)
The α, β-unsaturated ketones of IV) are reacted with the thiophenols of the formula (VI) in 1 to 5 molar equivalents, preferably 1.0 to 1.5 molar equivalents.

The following steps 2 to 5 may be carried out in the same manner as in scheme 3, and the details are omitted. Next, the compound (XIXa) obtained in step 3 or 5 is reacted in the same manner as in the above-mentioned production scheme 1 or 2, to obtain an aromatic carboxylic acid derivative of the formula (IIx).

(Step 1) Formula (XVI) obtained by Step 1 of Production Scheme 5
In this step, the sulfides of a) are reduced to alcohols of the formula (XVIIb). The reducing agent to be used is not particularly limited, but it is preferable to use sodium borohydride. Sodium borohydride has the formula (XVIa)
The solvent is preferably used in an amount of 0.25 to 1.0 mole equivalent to the sulfides, and the solvent is preferably an alcoholic solvent such as methanol or ethanol. The reaction generally proceeds smoothly within the range of 0 ° C. to room temperature and does not require any particular heating.

The following steps 2, 3, and 4 correspond to step 3 of production scheme 3,
The steps may be performed in the same manner as in steps 4 and 5, and the details are omitted. Next, the compound (XIX b) obtained in step 3 or 4 is reacted in the same manner as in the above production scheme 1 or 2, and the compound of formula (II)
An aromatic carboxylic acid derivative of x) is obtained.

The compounds of general formula p is 0 among the aromatic carboxylic acid derivative represented by (II) (where never X ² and X ⁵ to form a bond with each other) or aromatic represented by the general formula (II y) Aromatic carboxylic acid derivatives are prepared according to the following production schemes 7 to
It is manufactured by the method represented by 10.

(Step 1) Step 1 is a reaction in which a substituted thiophenol (VI) is reacted with a halogenated olefin (XXV) as an alkylating agent in the presence of a base to alkylate to obtain an alkyl-substituted thiophenol (XXVI).

As the base used in this reaction, anhydrous potassium carbonate,
Inorganic bases such as sodium hydroxide and potassium hydroxide, and organic bases such as triethylamine are exemplified, and anhydrous potassium carbonate is preferred. The amount of the base used is generally 0.5 to 3.0 equivalents, preferably 1.0 to 1.2 equivalents, relative to the substituted thiophenol (VI).

The alkylating agent used in this reaction, the halogenated olefin (XXV), is generally used in an amount of 1.0 to 2.0 equivalents, preferably 1.0 to 1.2 equivalents, based on the substituted thiophenol (VI).

The reaction solvent is not particularly limited as long as it is inert to the reaction, but acetone, dimethylformamide (DMF) and the like are preferable. The reaction time is 10 minutes to 8 hours.
Complete in about an hour. The reaction temperature can be arbitrarily selected from 0 ° C to the reflux temperature of the solvent, but is preferably from room temperature to 60 ° C.

After completion of the reaction, the reaction solution is cooled, insolubles are removed, and the solvent is distilled off. The residue is redispersed in an organic solvent such as hexane,
After washing and drying, the solvent is distilled off, whereby the alkyl-substituted thiophenol (XXVI) can be isolated.

(Step 2) In the step 2, an alkyl-substituted thiophenol (XXVI) is cyclized by an intramolecular Friedel-Crafts reaction in the presence of a dehydration condensing agent to give a hydrobenzo [b] thiophene compound (XX
VII).

As the dehydrating condensing agent used in this reaction, for example, sulfuric acid,
Phosphoric acid, phosphorus pentoxide, polyphosphoric acid and the like can be mentioned, and polyphosphoric acid is preferable. The dehydrating condensing agent is generally used in an amount of usually 1 to 10 molar equivalents relative to the alkyl-substituted thiophenol (XXVI).

The reaction temperature ranges from room temperature to 200 ° C., but is usually 100
~ 150 ° C is preferred. The reaction time is from 30 minutes to 16 hours, but preferably from 2 to 8 hours.

After completion of the reaction, the reaction solution is poured into ice water, a solvent such as hexane is added, and the mixture is separated. The obtained organic layer is washed, dehydrated, and then the solvent is distilled off. The resulting residue is purified by a means such as column chromatography using a developing solvent such as hexane to isolate the hydrobenzo [b] thiophene compound (XXVII).

(Step 3) In step 3, the hydrobenzo [b] thiophene compound (XX
VII) is reacted with a halogenating reagent such as bromine, sulfuryl chloride or chlorine in the presence of a solvent such as methylene chloride, chloroform or carbon tetrachloride to form a benzo [b] thiophene ring 5
This is a reaction for obtaining a halogenated benzo [b] thiophene compound (XXVII) substituted at the halogen position.

The amount of the halogenating reagent used in this reaction is generally 1. to the hydrobenzo [b] thiophene compound (XXVIII).
It is 0 to 3.0 equivalents, preferably 1.0 to 1.5 equivalents. The reaction temperature is usually preferably from 0 to 80 ° C, and the reaction time is usually preferably from about 1 to 80 hours.

After completion of the reaction, the excess halogenating reagent is removed with an aqueous solution of sodium bisulfite or the like, and post-treatment is carried out according to a conventional method to carry out the desired halogenated benzo [b] thiophene compound (XXVI
II) can be isolated.

(Step 4) Step 4 is a step wherein halogenated benzo [b] thiophene (XXVI
II) is reacted with magnesium (Mg) to give a Grignard reagent, which is then reacted with carbon dioxide (CO ₂ ) to give an aromatic compound of formula (IIy) having a carboxyl group introduced at the 5-position of the hydrobenzo [b] thiophene ring. This is a reaction to obtain a compound (XXIX) (n = 0, sulfide compound) which is an aromatic carboxylic acid derivative. It is preferable to use ethers such as diethyl ether and tetrahydrofuran as the solvent. The reaction temperature is preferably from 0 to 70C, particularly preferably from 20 to 60C. The reaction time is
Usually, it is about 1 to 7 hours.

The amount of magnesium (Mg) for obtaining the Grignard reagent is preferably 1.1 to 3.5 molar equivalents relative to the halogenated hydrobenzo [b] thiophene compound (XXVIII). The Grignard reaction is preferably performed in the presence of an alkyl iodide such as methyl iodide or an alkyl bromide such as ethyl bromide, since the reaction proceeds smoothly. The amount of the alkyl halide used at this time is preferably from 0.1 to 2.5 molar equivalents relative to the halogenated hydrobenzo [b] thiophene compound (XXVIII).

The reaction between Grignard reagent and carbon dioxide (CO ₂ ) can be performed by blowing carbon dioxide gas from a cylinder into the Grignard reagent in the solvent or dry ice (solid carbon dioxide).
This is performed by blowing in carbon dioxide gas generated from. Alternatively, dry ice may be added directly to the Grignard reagent for reaction.

After the reaction, an acid such as hydrochloric acid is added dropwise to the reaction solution to stop the reaction, an organic solvent such as ethyl acetate is added to separate the solution, and the obtained organic layer is separated by adding an alkali such as an aqueous potassium carbonate solution. The resulting aqueous layer is neutralized with an acid such as hydrochloric acid and extracted with an organic solvent such as ethyl acetate. After the obtained organic layer is washed and dried, the solvent is distilled off, whereby the compound (XXIX) (n = 0, sulfide compound) which is an aromatic carboxylic acid derivative of the formula (IIy) can be isolated. .

(Step 5) Step 5 comprises reacting the compound of formula (XXIX) with an oxidizing agent (eg, hydrogen peroxide, peracetic acid, sodium metaperiodate, etc.) in a solvent (eg, acetic acid, water, methanol, etc.). Compound (XX) which is an aromatic carboxylic acid derivative of (II y)
X) (n = 1, sulfoxide compound, n = 2, sulfone compound).

By reacting one equivalent of the oxidizing agent with respect to the compound (XXIX), sulfoxide (compound with n = 1) is reacted with at least two equivalents to obtain sulfone (compound with n = 2).

The reaction temperature of this reaction is usually from 25 to 110 ° C, preferably from 60 to 100 ° C. The reaction time is generally 30 minutes to 8 minutes.
The time is preferably 1 to 3 hours.

After completion of the reaction, the reaction solution is poured into an aqueous solution of sodium hydrogen sulfite or the like, an organic solvent such as ethyl acetate is added thereto, and the mixture is separated.The obtained organic layer is washed, dried, and then the solvent is distilled off. The compound of formula (XXX) can be isolated.

The starting material, a hydrobenzo [b] thiophene compound of the formula (XXVII), is obtained by steps 1 and 2 of production scheme 7. Hereinafter, Steps 1, 2, 2 'and 3 are essentially the same reactions as Steps 3, 4, 4' and 5 of Production Scheme 2, respectively, and the details are omitted.

(Step 1) Step 1 is a step of substituting a substituted thiophenol (VI) in the presence of a base.
And the α-halo-carbonyl compound (XXXIII) to obtain a compound of the formula (XXXIV).

Examples of the base used in this reaction include inorganic bases such as anhydrous potassium carbonate, sodium hydroxide and potassium hydroxide, and organic bases such as triethylamine, and anhydrous potassium carbonate is preferable. The amount of the base used is generally 0.5 to 3.0 molar equivalents relative to the substituted thiophenol (VI), and 1.
0-1.2 molar equivalents are preferred.

The α-halo-carbonyl compound (XXXIII) is usually used in an amount of 1.0 to 2.0 molar equivalents, preferably 1.0 to 1.2 molar equivalents, based on the substituted thiophenol (VI).

The reaction solvent is not particularly limited as long as it is inert to the reaction. For example, acetone, dimethylformamide (DMF) and the like are suitable.

The reaction temperature can be arbitrarily selected from 0 ° C to the reflux temperature of the solvent, but is preferably from room temperature to 60 ° C. The reaction time is 10 minutes to 8 hours, but is usually completed in about 2 hours.

After completion of the reaction, the reaction solution is cooled, insolubles are removed, and the solvent is distilled off. The obtained residue is redispersed in a solvent such as hexane, washed and dried, and then the solvent is distilled off to isolate Compound (XXXIV).

(Step 2) Step 2 is performed in the presence of a dehydrating agent and / or an acid catalyst.
Benzo [b] thiophene compound (XXXV) by subjecting the compound (XXXIV) obtained in
Is a reaction that forms

Examples of the dehydrating agent used in this reaction include sulfuric acid, phosphoric acid, phosphorus pentoxide, polyphosphoric acid, and the like, and polyphosphoric acid is preferable. Examples of the acid catalyst include p-toluenesulfonic acid, methanesulfonic acid, and trifluoromethanesulfonic acid, and trifluoromethanesulfonic acid is preferred. The dehydrating agent and / or the acid catalyst is a compound (XXXIV)
Is generally used in an amount of 1 to 10 molar equivalents, preferably 1.0 to 3.0 molar equivalents.

The reaction temperature can be arbitrarily selected from 0 ° C. to the reflux temperature of the solvent, but is usually preferably from room temperature to 60 ° C. Reaction time is 10 minutes to 8
It takes about two hours to complete the process.

After completion of the reaction, the reaction solution was poured into ice water according to a conventional method, and the precipitated white crystals were redispersed in an organic solvent such as n-hexane.
By distilling off the solvent after washing, the benzo [b] thiophene compound (XXXV) can be isolated.

(Step 3) In step 3, the benzo [b] thiophene compound (XXXV) obtained in step 2 is reduced, and hydrobenzo [b] thiophene in which the double bond between the 2- and 3-positions of the thiophene ring is reduced. This is a reaction for obtaining the compound (XXVIIa).

The method of reduction is not particularly limited, but a method of reducing with normal or pressurized hydrogen in the presence of a catalyst such as palladium or platinum oxide is simple and preferred.

After completion of the reaction, the catalyst is removed and the solvent is distilled off according to a conventional method to distill the desired hydrobenzo [b] thiophene compound (XXVI
Ia) can be isolated.

Hereinafter, the halogenation reaction, Grignard reaction, and oxidation reaction are achieved in the same manner as in Steps 3, 4, and 5 of Production Scheme 7, and the desired aromatic carboxylic acid derivative (IIy) is obtained.

The aromatic carboxylic acid derivative represented by the general formula (IIy) is generally produced by a method represented by the following production scheme 10.

(Step 1) A thiophenol of the formula (VI) is reacted with a ketone of the formula (XXXIIIa) in the same manner as in the above-mentioned Production Scheme 9 to produce a sulfide of the formula (XXXIVa). .

(Step 2) In this step, a Grignard reagent is reacted with the sulfide of the formula (XXXIVa) obtained in the step 1 to give an alcohol of the formula (XXXVI). This step is a typical Grignard reaction, and details are omitted.

The following steps 3, 4, and 5 correspond to step 3 of production scheme 3,
The steps may be performed in the same manner as in steps 4 and 5, and the details are omitted. Then, for the compound (XXXVIIb) obtained in step 3 or 5,
The reaction is carried out in the same manner as in the above Production Scheme 7, to obtain an aromatic carboxylic acid derivative of the formula (IIy).

Among the aromatic carboxylic acid derivatives represented by the general formula (II), the aromatic carboxylic acid derivative wherein X ⁴ is hydrogen can be produced by the following production scheme 11.

(Steps 1 and 2) Steps 1 to 3 of production scheme 1, or production scheme 4,
Formula (XXXVII) obtained by Steps 1-3 of Scheme 7
The starting material of I) is prepared as described in steps 4 and 5 of Production Scheme 1.
In the same manner as described above, an aromatic carboxylic acid derivative represented by the formula (XXXIX) (n = 0, a sulfide compound) is converted to a compound represented by the formula (XX).
XX) (n = 1, sulfone compound / n = 2, sulfoxide compound). See the description in Production Scheme 1 for details of the reaction.

(Step 3) In this step, the compound of the formula (XXXX) is reduced to an aromatic carboxylic acid derivative (n = 1 or 2) represented by the formula (XXXXI). Although there is no particular limitation on the reduction method, for example, in the presence of a catalyst such as palladium or platinum oxide, a method of reducing using hydrogen under normal pressure or pressure, or without using a catalyst, directly using zinc dust There is a way to reduce. In order to capture hydrogen chloride generated by the reaction, a base such as triethylamine, pyridine, sodium hydroxide, potassium hydroxide or the like is coexisted in an equivalent amount or more with respect to the compound of the formula (XXXX). As the solvent, alcoholic solvents such as methanol and ethanol are preferable, but in order to sufficiently dissolve the starting materials, it is most preferable to use about 60% aqueous ethanol. The reaction temperature is usually 20-120 ° C, and the reaction time is usually 1-1.
It takes about 2 hours.

An aromatic carboxylic acid derivative in which p is 1 and X ² and X ⁵ together form a bond, that is, a compound represented by the formula (IIza), is produced by the following Scheme 12 or 13.

(Step 1) A benzoic acid ester represented by the formula (XXXXII) is condensed with a mercaptopropionic acid derivative represented by the formula (XXXXIII) to form a phenylthiopropionic acid derivative represented by the formula (XXXXIV). This is the step of performing This step is N
It is preferably carried out in an aprotic polar solvent such as -methylpyrrolidone or N, N-dimethylformamide in the presence of a base. Examples of the base used include potassium carbonate, sodium carbonate and the like. The base is used in an amount of 1.0 to 3.0 molar equivalents relative to the benzoate. The reaction temperature can be from room temperature to the boiling point of the solvent, preferably from 80 ° C to 130 ° C.
It is. The reaction time is usually 1 to 8 hours.

(Step 2) In this step, the phenylthiopropionic acid derivative (XXXXIV) obtained in Step 1 is condensed and cyclized to give a thiochroman-4-one derivative of the formula (XXXXV).

As the condensation method, for example, (i) the phenylthiopropionic acid derivative (XXXXIV) is converted into hydrogen fluoride, sulfuric acid, phosphorus pentachloride, phosphoric acid, polyphosphoric acid, tin chloride, zinc chloride, aluminum chloride, Amberlyst (an ion exchange resin). (Ii) phenylthiopropionic acid derivative (XXXXIV) is reacted with, for example, a chlorinating agent of the thionyl chloride group to form an acid chloride,
A method in which cyclization is carried out in the presence of an acid catalyst similar to the above method (i) is exemplified. The solvent used in the reaction is not particularly limited as long as it is inert under the reaction conditions, but hydrocarbon solvents such as pentane and hexane, dichloromethane, 1,1, and the like.
Halogen solvents such as 2-dichloroethane are preferred. Further, a method using polyphosphoric acid as a solvent and an acid catalyst is also suitable. In the condensation cyclization method (i), the acid catalyst is used in an amount of 0.01 to 20 molar equivalents, preferably 1.0 to 10 molar equivalents, based on the phenylthiopropionic acid derivative (XXXXIV). The reaction temperature is usually in the range of room temperature to 120 ° C, preferably 50 to 100 ° C. The reaction time is usually from 30 minutes to 8 hours, preferably from 30 minutes to 2 hours. The above (i
In the condensed cyclization method i), the chlorinating agent is used in an amount of 1.0 to 3.0 molar equivalents, preferably 1.1 to 1.5 molar equivalents, based on the phenylthiopropionic acid derivative (XXXXIV). The reaction temperature of the reaction with the acid chloride is usually in the range of 0 to 120 ° C,
Preferably it is from room temperature to the reflux temperature of the solvent. The reaction time is usually 30 minutes to 8 hours, preferably 30 minutes to 2 hours. The acid catalyst used in the cyclization method (ii) is used in an amount of 0.01 to 1.0 molar equivalent, preferably 0.1 to 1.0 molar equivalent, based on the acid chloride. The reaction temperature of the reaction using an acid catalyst is usually room temperature to 12
The temperature is 0 ° C., preferably room temperature to 80 ° C. The reaction time is usually from 30 minutes to 8 hours, preferably from 2 to 4 hours.

(Step 3) The thiochroman-4-one derivative (XX) obtained in Step 2
XXV) to obtain a hydroxythiochroman derivative represented by the formula (XXXXVI).

Although there is no particular limitation on the reduction method, (i) a method using a reducing agent such as sodium borohydride in a solvent inert to the reaction such as alcohol or dichloromethane,
(Ii) a method of hydrogenating at normal pressure or under pressure in the presence of a reducing catalyst such as palladium or nickel. In the above reduction method (i), the reducing agent is used in an amount of 1.0 to 5.0 molar equivalents, preferably 1.1 to 2.0 molar equivalents, relative to the thiochroman-4-one derivative (XXXXV). Reaction temperature is usually -20 to 50
° C, but preferably from 0 to 20 ° C. The reaction time is usually 30 minutes to 8 hours, preferably 30 minutes to 2 hours. In the above reduction method (ii), the reducing agent is 1 to 50% by weight based on the thiochroman-4-one derivative (XXXXV),
Preferably, 10 to 20% by weight is used. The hydrogen pressure is usually from normal pressure to 100 kg / cm ² , preferably from 10 to 50 kg / cm ² . The reaction temperature is from room temperature to 100 ° C, and the reaction time is from 1 to 8
Time.

As a preferred embodiment of the reaction in Step 3, there is a method in which ethanol and dichloroethane are used as solvents and reduction is performed using sodium borohydride. In this case, the reaction temperature is preferably 0 ° C. to room temperature, and the reaction time is preferably 30 minutes to 2 hours.

When the reduction reaction is performed with sodium borohydride, after the reaction is completed, the reaction solution is poured into ice water and extracted with dichloromethane. The obtained organic layer is washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent is distilled off to obtain a crude product. The crude product can be directly used for the next reaction without purification.

(Step 4) Step 4 is a step of oxidizing the hydroxythiochroman derivative (XXXXVI) obtained in Step 3 to obtain hydroxythiochroman oxide (XXXXVII). The same oxidation reaction may be performed according to this, and the details are omitted.

(Step 5) Step 5 is a step of dehydrating the hydroxythiochroman oxide (XXXXVII) obtained in Step 4 to obtain 3,4-dehydrothiochromans (XXXXVIII). The dehydration reaction is the same as in step 2 of step 2, and may be performed according to this, and the details are omitted.

(Step 6) Step 6, obtained in Step 5 3,4-dehydro loti octene Romain such a (XXXXVIII) is hydrolyzed in the step of obtaining object of aromatic carboxylic acids (II za, X ³ = hydrogen) and is there. This is a well-known ester hydrolysis reaction, and the details are omitted. This step can be performed prior to step 4 or step 5.

Via steps 1a, 2a, an aromatic carboxylic acid derivative of formula (II za) wherein R ³ is a C ₁ -C ₄ alkyl group is obtained,
Formula (II z) wherein R ³ is hydrogen via Steps 1b and 2b
The aromatic carboxylic acid of a) is obtained.

Steps 1a and 2a are essentially the same as step 1 or 2 of scheme 4, respectively, and details are omitted.

(Step 1b) In this step, the brominated thiochroman-4-one compound (XX) is reduced to a brominated thiochroman-4-ol compound (XXIb).

Examples of the reducing agent used here include lithium aluminum hydride and sodium borohydride. The reducing agent is a brominated thiochroman-4-ol compound (XXIb)
Is generally used in an amount of 0.3 to 1.2 equivalents, preferably 0.5 to 1.0 equivalents.

The reaction temperature is generally 0 to 60 ° C, preferably 0 to 60 ° C.
~ 10 ° C. The reaction time is generally 10 minutes to 8 hours, but is usually completed in 10 minutes to 2 hours.

After completion of the reaction, an acid such as dilute hydrochloric acid is added to the reaction solution, and an organic solvent such as ethyl acetate is added to the reaction solution to carry out liquid separation. After the obtained organic layer is washed and dried, the solvent is distilled off to obtain the desired brominated thiochroman-4-ol compound (XXIb).
Can be isolated.

Step 2b is essentially the same as step 2 in scheme 4,
Details are omitted.

Steps 3 and 4 are essentially the same reactions as Steps 4 or 5 of Scheme 1, respectively, and details are omitted.

The aromatic carboxylic acid derivative (II) in which p is 0 and X ² and X ⁵ together form a bond, that is, the compound represented by the formula (II zb), is produced by the following Scheme 14.

A bromine-substituted thiophenol derivative represented by the formula (VI-Br) is used as a starting material instead of the substituted thiophenol represented by the formula (VI) in Scheme 9. This bromine-substituted thiophenol derivative can also be obtained by a known method similar to the substituted thiophenol of the formula (VI).

Hereinafter, Steps 1 and 2 are essentially the same reaction as Steps 1 and 2 in Scheme 9, respectively, and Steps 3 and 4 are the same as Steps 4 and 5 in Scheme 7, respectively, and the details are omitted.

Among the novel pyrazole derivatives of the present invention, the pyrazole derivative represented by the general formula (If) or (Ig) wherein p is 1 and both X ² and X ⁵ are hydrogen can be prepared by the following method. can get.

(Step 1) In this step, the pyrazole derivative of the formula (Ie) is reduced to a pyrazole derivative (If) of the present invention. As a reduction method, it is preferable to use a hydrogen such as a normal pressure or a pressurized hydrogen under a catalyst such as palladium or platinum oxide. The amount of the catalyst used is preferably 5 to 20% by weight based on the pyrazole derivative of the formula (Ie), and it is preferable to use an alcoholic solvent such as methanol or ethanol as a solvent. The reaction temperature is from room temperature to about 80 ° C., but usually the reaction proceeds smoothly at room temperature. The reaction time is about 2 hours to 24 hours.

(Step 2) Step 2 is a step of obtaining a pyrazole derivative (Ig) by reacting the pyrazole derivative (If) with Q ¹ -Hal, and is a step 2 of the pyrazole derivative production method (1).
It is basically the same as above, so please refer to the description of this part.

The 5-hydroxypyrazole represented by the general formula (III), which is a starting material for producing the pyrazole derivative (I) of the present invention, can be produced by any of the following methods depending on the substituent. it can. In the following reaction formula, R ¹
And R ² are as defined in general formula (I).

The above (1) to (3) are methods for producing 5-hydroxypyrazoles of the general formula (III) wherein R ² = hydrogen atom, and the above (4) and (5) are for R ² = C ₁ to C ₄ alkyl group, C ₁ -C ₄ haloalkyl group or
A C ₂ -C ₄ alkoxycarbonyl method for producing 5-hydroxypyrazole of the general formula is an alkyl group (III).

The following Table 1 shows examples of the pyrazole derivatives included in the formula (I) of the present invention when p = 0 and X ⁵ = X ⁶ = hydrogen atom. However, the present invention is not limited to this.

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Step (1) 2,5-dimethylthiophenol is placed in a 100 ml eggplant flask.
6.9 g (50 mmol), 5.5 g (60 mmol) of methallyl chloride, a halogenated olefin, 1.2 equivalent), 6.9 g (50 mmol, 1 equivalent) of potassium carbonate and 30 ml of acetone
And heated under reflux for 1 hour. After allowing the reaction solution to cool, insolubles were removed by filtration, and acetone was distilled off. The obtained residue was redispersed in n-hexane and washed with saturated saline. After the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off to obtain 8.6 g of 2-methyl-3- (2,5-dimethylphenylthio) -1-propene (89% yield).

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.87 (3H, s), 2.28 (3H, s), 2.3
3 (3H, s), 3.49 (2H, s), 4.87 (2H, m), 6.8-7.3 (3
H, m) IR (KBr tablet, cm ^-1 ): 3090, 2980, 1610 Step (2) In a 100 ml eggplant flask, add the 2-methyl-3- (2,5-dimethylphenylthio) obtained in the above step (1). ) 8.6 g (45 mmol) of 1-propene, 50 g of polyphosphoric acid as a dehydrating condensing agent
(Containing 300 mmol (6.7 equivalents) of diphosphorus pentoxide (P ₂ O ₅ ))
And reacted at 150 ° C. for 2 hours. After completion of the reaction, the reaction solution was poured into ice water and extracted with n-hexane. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The crude product obtained by removing the solvent was purified by column chromatography (elution solvent: n-hexane) and 1.6 g of 3,3,4-tetramethyl-2-hydrobenzo [b] thiophene (yield 19) %).

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.45 (6H, s), 2.21 (3H, s), 2.3
6 (3H, s), 3.08 (2H, s), 6.80 (2H, dd) IR (KBr tablet, cm ^-1 ): 2970, 1465, 800 Step (3) Obtained in the above step (2) in a 100 ml eggplant flask. 3,3,4,7−
1.6 g of tetramethyl-2-hydrobenzo [b] thiophene
(8 mmol) and 30 ml of cocoloform were added thereto, and 0.55 ml (10.7 mmol, 1.34 equivalent) of bromine was added dropwise thereto. After reacting at room temperature for 1 hour, the reaction solution was washed sequentially with an aqueous solution of sodium hydrogen sulfite and a saturated saline solution, and dried over anhydrous sodium sulfate. The solvent was distilled off and 5-bromo-3,3,4,7
-Tetramethyl-2-hydrobenzo [b] thiophene 1.
9 g (85% yield) was obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.48 (6H, s), 2.18 (3H, s), 2.4
1 (3H, s), 3.08 (2H, s), 7.20 (1H, s) IR (KBr tablet, cm ^-1 ): 2950, 1440, 1100 Step (4) In a 100 ml three-necked flask, THF 30 ml, magnesium 0.7 g
(24 mmol, 3.4 equivalents) and 1.52 g (14
Mmol, 2 equivalents) was added dropwise and activated, followed by THF5ml
5-bromo-3,3,4, obtained in the above step (3) dissolved in
7-tetramethyl-2-hydrobenzo [b] thiophene
1.9 g (7.0 mmol) was added dropwise, and the mixture was heated under reflux for 4 hours.
After allowing to cool to room temperature, carbon dioxide gas was bubbled for 2 hours. The reaction was stopped by adding 5% hydrochloric acid dropwise to the reaction solution, and extracted with ethyl acetate. The obtained organic layer was extracted with an aqueous solution of potassium carbonate, and the obtained aqueous layer was washed with ethyl acetate, neutralized with 5% hydrochloric acid, and extracted with ethyl acetate. After the obtained organic layer was washed with a saturated saline solution, it was dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 3,3,4,7-tetramethyl-.
2-hydrobenzo [b] thiophene-5-carboxylic acid 1.
2 g (70% yield) was obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.51 (6H, s), 2.22 (3H, s), 2.5
8 (3H, s), 3.12 (2H, s), 7.62 (1H, s) IR (KBr tablet, cm ^-1 ): 3500, 3000, 1690 Step (5) In a 100 ml eggplant flask, the above step (4) 3,3,4,7-tetramethyl-2-hydrobenzo [b] thiophene-5-carboxylic acid of the aromatic carboxylic acid obtained in 1.2 g (4.9 mmol), 1.7 ml of 30% H ₂ O ₂ (15.0 mmol, 3.1 equivalents) and 10 ml of acetic acid, and reacted at 100 ° C. for 2 hours. The reaction solution was poured into an aqueous solution of sodium hydrogen sulfite, and extracted with ethyl acetate. The obtained organic layer was washed with a saturated saline solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to remove 3,3,4,7-tetramethyl-2-hydrobenzo [b] thiophen-5-.
1.0 g (79% yield) of carboxylic acid-1,1-dioxide was obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.69 (6H, s), 2.63 (6H, s), 3.3
8 (2H, s), 7.30 (1H, s), 7.72 (1H, s) IR (KBr tablet, cm ^-1 ): 3450, 1740 Step (1) Methyl magnesium bromide (MeMgB
55 ml (55 mmol, 3 equivalents) of a 1M solution of r) and 100 ml of tetrahydrofuran (THF) were added, and the mixture was ice-cooled under a nitrogen stream. A solution of 5.0 g (18.4 mmol) of 6-bromo-5,8-dimethylthiochroman-4-one dissolved in 15 ml of THF was added dropwise thereto, followed by stirring at room temperature for 3 hours and refluxing for 2 hours. 5% HCl was added to the reaction solution, and extracted with ethyl acetate. The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off, and 5.2 g of 6-bromo-4,5,8-trimethylthiochroman-4-ol (99% yield) ) Got.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.60 (3H, s), 2.20 (3H, s), 2.2
6-2.36 (2H, m), 2.70 (3H, s), 2.80-3.10 (2H,
m), 7.40 (H, s) Step (2) 5.4 g (18.8 mmol) of 6-bromo-4,5,8-trimethylthiochroman-4-ol obtained in the above step (1), 100 ml of benzene, p- Toluenesulfonic acid 10 mg (0.06 mmol, 0.0032 equivalent) was added to a Dean-Stark tube 20
It was charged into a 0 ml flask and heated under reflux for 1 hour. After cooling, the reaction solution was washed successively with an aqueous solution of sodium hydrogen carbonate and a saturated saline solution, and dried over anhydrous sodium sulfate. The residue (crude product) obtained by distilling off the solvent was purified by silica gel column chromatography (developing solvent: hexane, ethyl acetate) to give 6-bromo-4,5,8-trimethyl-.
1.4 g (yield 27%) of 3,4-dehydrothiochroman was obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 2.08 (3H, s), 2.29 (3H, s), 2.4
2 (3H, s), 2.99 (2H, dd), 6.02 (1H, t), 7.22 (1H,
s) Step (3) In a 100 ml portable reactor, 6-bromo-4,5,8-
1.32 g of trimethyl-3,4-dehydrothiochroman, 5% Pd
/ C 0.55 g, chloroform 20 ml, hydrogen pressure 5 kg / cm ²
The reaction was carried out at room temperature under a gauge for 6 hours. After completion of the reaction, the catalyst was filtered off and the solvent was distilled off to give 6-bromo-4,5,8.
1.21 g (91% yield) of trimethylthiochroman were obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.15 (3H, d), 2.20 (3H, s), 2.3
8 (3H, s), 1.8-2.3 (H, m), 2.9-3.1 (2H, m), 3.2
-3.4 (2H, m) 7.20 (H, s) Step (4) In a 50 ml three-necked flask, THF 15 ml, magnesium 0.43 g
(18 mmol), 0.97 g (9 mmol) of ethyl bromide was added dropwise, activated, and then dissolved in 3 ml of THF.
1.21 g of bromo-4,5,8-trimethylthiochroman (4.
(5 mmol) was added dropwise, and the mixture was heated under reflux for 6 hours. After allowing to cool to room temperature, CO ₂ gas was bubbled for 2 hours. The reaction was stopped with 5% hydrochloric acid and extracted with ethyl acetate. The organic layer was extracted with an aqueous solution of potassium carbonate, and the aqueous layer was washed with ethyl acetate.
And neutralized with hydrochloric acid. The generated carboxylic acid was extracted with ethyl acetate, washed with saturated saline, and dried over sodium sulfate. The solvent was distilled off to obtain 0.75 g (yield 71%) of 4,5,8-trimethylthiochroman-6-carboxylic acid.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.14 (3H, d), 2.23 (3H, s), 1.7
5 to 2.35 (H, m), 2,55 (3H, s), 2.9 to 3.1 (2H, m), 3.
2-3.5 (2H, m), 7.60 (H, s) Step (5) 0.75 g (3.2 mmol) of 4,5,8-trimethylthiochroman-6-carboxylic acid in a 30 ml eggplant flask, 30% peroxide 1.1 g of hydrogen (9.5 mmol, 3 equivalents) and 1 ml of acetic acid were added.
The reaction was performed at 100 ° C. for 2 hours. The reaction solution was poured into an aqueous solution of sodium hydrogen sulfite, and extracted with ethyl acetate. After washing with saturated saline, drying over sodium sulfate, the solvent was distilled off, and 4,5,8-trimethylthiochroman-6-carboxylic acid-
0.71 g (98% yield) of 1,1-dioxide was obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.35 (3H, d), 2.0 to 2.4 (H, m),
2.57 (3H, s) 2.77 (3H, s), 3.3 to 3.8 (4H, m), 7.67
(H, s) Step (1) Triethylamine was added to a mixture of 10.0 g (72.5 mmol) of 2,5-dimethylthiophenol, 7.32 g (87.0 mmol) of ethyl vinyl ketone and 30 ml of dichloroethane.
5 ml was added and stirred for 1 hour. The mixture was diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to give (2,5-dimethylphenyl) -3-oxopentyl sulfide. 16.1 g (100% yield) was obtained as a colorless and transparent oil.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.05 (3H, t, J = 7 Hz), 2.31 (6H,
s), 2.43 (2H, q, J = 7Hz), 2.6-2.9 (2H, m), 3.0-
3.3 (2H, m), 6.9-7.2 (3H, m) Step (2) 16.1 g (72.6 mmol) of (2,5-dimethylphenyl) -3-oxopentyl sulfide and 64 ml of ethanol in 1.65 g of sodium borohydride ( (43.6 mmol) was slowly added at 0 ° C., and the mixture was stirred at room temperature for 1 hour. Mix the mixture with ice and 5%
Poured into aqueous hydrochloric acid and extracted with dichloroethane. The extract was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure to give (2,5-dimethylphenyl) -3.
-16.3 g of hydroxypentyl sulfide was obtained as a colorless and transparent oil.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 0.95 (3H, t), 1.3 to 1.9 (4H,
m), 2.31 (6H, s), 2.9-3.1 (2H, m), 3.6-3.9 (H,
m), 6.8 to 7.2 (3H, m) Step (3) 10.0 g (45.2 mmol) of (2,5-dimethylphenyl) -3-hydroxypentyl sulfide and dichloroethane 3
4.94 ml (67.8 mmol) of thionyl chloride in 0 ml of mixed solution
Was gradually added dropwise, followed by stirring at 60 ° C. for 2 hours. The reaction mixture was cooled to room temperature, and the solvent was distilled off under reduced pressure. Dichloromethane was added to the obtained residue, washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure to obtain crude (2,5-dimethylphenyl) -3-. 10.9 g of chloropentyl sulfide (yield 9
9%). This compound was used for the next reaction without further purification.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.03 (3H, t), 1.5 to 2.4 (4H,
m), 2.32 (6H, s), 2.8-3.2 (2H, m), 3.9-4.2 (H,
m), 6.8-7.2 (3H, m) Step (4) A mixed solution of 9.40 g (38.7 mmol) of (2,5-dimethylphenyl) -3-chloropentyl sulfide in dichloromethane was added to 5.18 g (38.7 mmol) of aluminum chloride. And 20 ml of methylene chloride were gradually added dropwise at 0 ° C.
The mixture was stirred at C for 2 hours, and further stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography (silica gel; hexane → hexane / ethyl acetate = 20: 1), and 3.64 g of 4-ethyl-5,8-dimethylthiochroman was purified.
(47% yield) as a brown oil.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 0.9 to 1.1 (3H, m), 1.4 to 2.5 (10
H, m), 2.8-4.1 (3H, m), 6.8-7.2 (2H, m) Step (5) 1.49 g (11.1 mmol) of aluminum chloride, 0.82 ml (11.6 mmol) of acetyl chloride and 6 ml of dichloromethane
Was added dropwise at 0 ° C. to a mixed solution of 1.91 g (9.26 mmol) of 4-ethyl-5,8-dimethylthiochroman and dichloromethane, and the mixture was further stirred for 1.5 hours. The reaction mixture was poured into ice and 5% aqueous hydrochloric acid and extracted with dichloromethane. Wash the extract with saturated aqueous sodium bicarbonate,
It was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure to give 6-acetyl-4-ethyl-5,8-.
1.66 g (yield 72%) of dimethylthiochroman was obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 0.99 (3H, t), 1.3 to 1.8 (2H,
m), 2.2-2.6 (2H, m), 2.25 (3H, m), 2.38 (3H,
s), 2.53 (3H, s), 2.8 to 3.8 (3H, m), 7.21 (H, s) Step (6) 1.66 g (6.68 mmol) of 6-acetyl-4-ethyl-5,8-dimethylthiochroman , 30% aqueous hydrogen peroxide solution 2.2
A mixed solution of 8 g (20.1 mmol) and 2.0 ml of acetic acid at 80 ° C
For 2 hours. Cool the mixture to room temperature,
A 2% aqueous sodium hydrogen sulfite solution was added, and the mixture was extracted with ethyl acetate, washed with a saturated aqueous sodium hydrogen carbonate solution and then with a saturated saline solution, and the organic layer was dried over anhydrous sodium sulfate.
After filtration, the solvent was distilled off under reduced pressure. The residue was subjected to column chromatography (silica gel; hexane / ethyl acetate = 2:
1) to give 1.03 g of 6-acetyl-4-ethyl-5,8-dimethylthiochroman-1,1-dioxide (yield 55
%).

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.53 (3H, t, J = 7 Hz), 1.42 (2H,
m), 2.2-2.6 (2H, m), 2.31 (3H, s), 2.53 (3H,
s), 2.75 (3H, s), 2.9 to 3.8 (3H, s), 7.20 (H, s) Step (7) 6-acetyl-4-ethyl-5,8-dimethylthiochroman-1,1-dioxide To a mixed solution of 1.03 g (3.67 mmol) and 4 ml of dioxane was added 13 ml of an aqueous solution of sodium hypochlorite dropwise at 0 ° C., and the mixture was stirred at 0 ° C. for 1 hour and further at room temperature overnight. To this mixture was added 5 ml of a 20% aqueous sodium sulfite solution, and the mixture was washed with dichloromethane. The aqueous layer was acidified with concentrated hydrochloric acid (pH 1), extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure to give 4-ethyl-5,8-dimethylthiochroman-.
0.90 g (87% yield) of 1,1-dioxide-6-carboxylic acid was obtained.

NMR (ppm, solvent: heavy acetone, internal standard: tetramethylsilane): 1.07 (3H, t), 1.5 to 1.8 (2H, m), 2.3
-2.7 (2H, m), 2.49 (3H, s), 2.69 (3H, s), 3.0-3.
9 (3H, m), 7.55 (H, s) Step (1) 4.0 g (29 mmol) of 2,5-dimethylthiophenol of a substituted thiophenol, α-halo-
3.2 g of chloroacetone chloroacetone (35 mmol,
1.2 equivalents), 4.0 g (29 mmol, 1 equivalent) of anhydrous potassium carbonate and 30 ml of acetone were added, and the mixture was heated under reflux for 2 hours.
After allowing the reaction solution to cool, insolubles were removed by filtration, and acetone was distilled off. The obtained residue was redispersed in n-hexane and washed with saturated saline. After the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off. 100 g of polyphosphoric acid as a dehydration condensing agent was added to the obtained residue, followed by stirring at room temperature for 1 hour. The reaction solution was poured into ice water, and the precipitated white crystals were redispersed in n-hexane and washed with saturated saline. The solvent was distilled off to obtain 4.5 g of 3,4,7-trimethylbenzo [b] thiophene (88% yield).

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 2.48 (3H, s), 2.62 (3H, s), 2.7
2 (3H, s), 2.98 (3H, s) Step (2) 3,4,7- obtained in the above step (1) in a 50 ml eggplant flask.
1.0 g of trimethylbenzo [b] thiophene, 30 ethanol
ml and 50 mg of platinum oxide were added and hydrogenated at normal pressure. After the completion of the reaction, the platinum oxide was removed by filtration, and ethanol was distilled off.
4,7-trimethyl-2-hydrobenzo [b] thiophene
0.94 g (93% yield) was obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.24 (3H, d), 2.21 (3H, s), 2.2
6 (3H, s), 2.7-3.1 (H, m), 3.4-3.8 (2H, m), 6.98
(3H, s) Step (3) 2.33 g (16.0 mmol, 1.2 equivalents) of aluminum chloride and 10 ml of dichloromethane were placed in a 100-ml eggplant-shaped flask and cooled with ice. To this, 1.15 ml (1.26 g, 17.5 mmol, 1.1 equivalent) of acetyl chloride was added dropwise, and the mixture was stirred at the same temperature under ice cooling for 15 minutes, and then 2.60 g of 3,4,7-trimethyl-2-hydrobenzo [b] thiophene ( 14.6 mmol) dichloromethane 10 ml
The solution was added dropwise.

After stirring for 30 minutes under ice-cooling, the mixture was stirred at room temperature for 3 hours, and poured into ice water to stop the reaction. The aqueous layer was extracted with dichloromethane, and the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off and 5-acetyl-3,4,7-
2.48 g of trimethyl-2-hydrobenzo [b] thiophene
(77% yield).

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.24 (3H, d), 2.25 (3H, s), 2.4
3 (3H, s), 2.54 (3H, s), 2.95 (H, d), 3.5-3.8 (2H,
m), 7.30 (H, s) Step (4) 2.48 g of 5-acetyl-3,4,7-trimethyl-2-hydrobenzo [b] thiophene (11.3
Mmol), 3.8 ml of 30% aqueous hydrogen peroxide and 3 ml of acetic acid, and reacted at 100 ° C. for 2 hours. The reaction solution was poured into an aqueous solution of sodium sulfite, and extracted with ethyl acetate. After washing with saturated saline, drying over sodium sulfate, the solvent was distilled off, and 2.67 g of 5-acetyl-3,4,7-trimethyl-2-hydrobenzo [b] thiophene-1,1-dioxide was obtained (yield: 94).
%).

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.50 (3H, d), 2.39 (3H, s), 2.5
7 (3H, s), 2.63 (3H, s), 3.25 (H, d), 3.5 to 3.75 (2
H, m), 7.37 (H, s) Step (5) 11.6 ml of 6.3% hypochlorous acid was charged into a 50 ml eggplant flask and cooled with ice. 5-acetyl-3,4,7-trimethyl-2
-Hydrobenzo [b] thiophene-1,1-dioxide 2.6
A solution of 7 g (10.6 mmol) in 10 ml of 1,4-dioxane was added dropwise. After the dropwise addition, the temperature was raised to room temperature, and the mixture was stirred for 3 hours. Thereafter, an aqueous solution of sodium sulfite was added, and the reaction solution was washed twice with methylene chloride, and then 10 ml of concentrated hydrochloric acid was added under cold water. After extracting three times with ethyl acetate, the extract was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 3,4,7-trimethyl-
2-hydrobenzo [b] thiophene-5-carboxylic acid-
2.38 g (88% yield) of 1,1-dioxide was obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.50 (3H, d), 2.58 (3H, s), 2.6
5 (3H, s), 3.28 (H, d), 3.5 to 3.75 (2H, m), 7.85
(H, s) Step (1) In a 100 ml eggplant flask, 5.0 g (18.4 mmol) of 6-bromo-5,8-dimethylthiochroman-4-one of a halogenated thiochroman-4-one compound is added to methanol.
Dissolve in 30ml and add sodium borohydride as reducing agent here
0.35 g (9.2 mmol, 0.5 eq) was added at room temperature. After stirring the reaction solution for 2 hours, dilute hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 0.49 g of 6-bromo-5,8-dimethylthiochroman-4-ol (95% yield).

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.8 to 3.3 (4H, m), 2.21 (3H,
s), 2.42 (3H, s), 5.06 (H, t), 7.30 (1 H, s) Step (2) 6-bromo-5,8-dimethylthiochroman-4-ol obtained in the above step (1) 4.0 g (16.6 mmol), 100 ml of benzene, 10 mg (0.06 mmol, 0.0036 equivalent) of p-toluenesulfonic acid were added to a 200 m tube equipped with a Dean-Stark tube.
The mixture was charged into a flask and heated under reflux for 1 hour. After cooling, the reaction solution was washed with an aqueous solution of sodium hydrogen carbonate and a saturated saline solution in that order, and dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 2.6 g of 6-bromo-5,8-dimethyl-3,4-dehydrothiochroman (69% yield).

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 2.30 (6H, s), 3.32 (2H, dd), 5.
9-6.2 (H, m), 6.6-7.0 (2H, m) Step (3) In a 200 ml three-necked flask, THF 50 ml, magnesium 0.56 g
(23 mmol, 1.2 equivalents), and one piece of iodine,
After activation by the dropwise addition of 5 drops of ethyl bromide, 4.88 g (19 mmol) of 6-bromo-5,8-dimethyl-3,4-dehydrothiochroman obtained in the above step (2) dissolved in 5 ml of THF. )
Was added dropwise, and the mixture was heated under reflux for 4 hours. After allowing the reaction solution to cool to room temperature, carbon dioxide gas was bubbled for 2 hours. The reaction was stopped by adding 5% hydrochloric acid dropwise to the reaction solution, and extracted with ethyl acetate. The obtained organic layer was extracted with an aqueous solution of potassium carbonate, the aqueous layer was washed with ethyl acetate, neutralized with 5% hydrochloric acid, and extracted with ethyl acetate. The obtained organic layer was washed with a saturated saline solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 5,8-dimethyl-3,4-dehydrothiochroman-6.
-1.9 g of carboxylic acid (46% yield) were obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 2.32 (3H, s), 2.60 (3H, s), 3.3
3 (2H, dd), 5.9-6.1 (H, m), 6.81 (H, d), 7.67 (H,
s) IR (KBr tablet, cm ^-1 ): 3300-2600, 1680 Step (1) 100 g of aluminum chloride as an acid catalyst (750 mmol,
1.21 equivalents) in a 250 ml solution of 1,2-dichloroethane, 80 ml of 3,4-dichlorotoluene which is a halogen-substituted benzene derivative
l (100 g, 621 mmol) was added and then 55 ml (774 mmol, 1.25 eq) of acetyl chloride, an acetylating agent, was added dropwise at room temperature. After completion of the dropwise addition, the reaction solution was stirred at room temperature for 10 minutes and then at 70 to 75 ° C for 5 hours. After cooling the reaction solution,
The mixture was gradually poured into 300 ml of ice water. Two-layer separation was performed, and the obtained organic layer was concentrated. The obtained aqueous layer was extracted with ethyl acetate, and the obtained organic layer was combined with the concentrated organic layer. The whole organic layer was washed once with 5% hydrochloric acid, twice with an aqueous sodium carbonate solution and once with a saturated saline solution, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and 125.1 g of a crude product of 3,4-dichloro-6-methylacetophenone (yield:
86%).

NMR (ppm, solvent: heavy acetone, internal standard: tetramethylsilane): 2.47 (3H, s), 2.58 (3H, s), 7.50
(H, s), 7.97 (H, s) Step (2) 1350% 12.9% sodium hypochlorite aqueous solution as oxidizing agent
ml (1.96 mol, 3 equivalents) was diluted with 400 ml of water and cooled to 8 ° C. under ice-cooling. Here, 3,4-dichloro-6-methylacetophenone 132.3 (65) obtained in the above step (1) was used.
(2 mmol) of a dioxane solution (130 ml) was added dropwise at 10 ° C. or lower, and dioxane (130 ml) was further added. Thereafter, the ice water bath was removed, and the mixture was stirred at room temperature. When the temperature in the reaction system reached 15 ° C., the mixture was again stirred under ice-cooling for 1 hour, and the ice-water bath was removed, followed by stirring at room temperature for 3.0 hours. Then, an aqueous solution of sodium sulfite 10.0 g (79 mmol) in 50 m
l was added. After the reaction solution was washed twice with methylene chloride, 170 ml of concentrated hydrochloric acid was added under ice cooling. After performing extraction three times with ethyl acetate, the obtained organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 3,4-dichloro-6.
119.3 g (83% yield) of a crude product of methylbenzoic acid was obtained.

NMR (ppm, solvent: acetone-d6, internal standard: tetramethylsilane): 2.59 (3H, s), 7.52 (H, s), 8.04
(H, s) Step (3) 92.1 g (421 mmol) of 3,4-dichloro-6-methylbenzoic acid obtained in the above step (2) is dissolved in 550 ml of ethanol, which is both an esterifying agent and a solvent, and the acid catalyst 20 ml of concentrated sulfuric acid
Was added and heated under reflux for 7 hours. After ethanol was distilled off under reduced pressure, ice water was added thereto, and the mixture was extracted twice with ethyl acetate. The obtained organic layer was washed sequentially with an aqueous sodium carbonate solution and saturated saline, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 103.4 g (yield: 97%) of a crude product of ethyl 3,4-dichloro-6-methylbenzoate.

NMR (ppm, solvent: heavy acetone, internal standard: tetramethylsilane): 1.39 (3H, t), 2.57 (3H, s), 4.35 (2
H, s), 7.52 (H, s), 7.98 (H, s) Step (4) 53.7 g (231 mmol) of ethyl 3,4-dichloro-6-methylbenzoate obtained in Step (3), To a solution of 37.0 g (268 mmol, 1.1 equivalents) of potassium carbonate in 215 ml of a N, N-dimethylformamide (DMF) solution at room temperature was added 23.4 ml (268 mmol, 1.1 equivalents) of 3-mercaptopropionic acid, and then 120-125. The mixture was heated with stirring at 200C for 2 hours and 20 minutes. The reaction solution was cooled to about 50 ° C., and ethyl acetate and water were added.
In order to remove neutral components, the resultant was washed four times with ethyl acetate and once with hexane. Concentrated hydrochloric acid was added to the obtained aqueous layer to precipitate crystals. After leaving for a while, the crystals were collected by filtration and washed three times with water. Dissolve the obtained crystals in ethyl acetate,
The obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 3- (2-chloro-4-ethoxycarbonyl-5-methylphenylthio) propionic acid crude. 50.4 g (60% yield) of the product was obtained.

NMR (ppm, solvent: heavy acetone, internal standard: tetramethylsilane): 1.38 (3H, t), 2.58 (3H, s), 2.79 (2
H, t), 3.25 (2H, t), 7.33 (H, s), 7.87 (H, s) Step (5) Heat 167 g of polyphosphoric acid, an acid catalyst, to 80 to 85 ° C,
To this, 47.7 g (157 mmol) of 3- (2-chloro-4-ethoxycarbonyl-5-methylphenylthio) propionic acid obtained in the above step (4) was added over 5 minutes.
The mixture was heated and stirred for 20 minutes. After allowing the reaction solution to cool to room temperature, it was gradually added to a mixture of 191 g (1.80 mol) of sodium carbonate and ice, and stirred at room temperature until sodium carbonate was almost dissolved. Extraction was performed twice with ethyl acetate, and the obtained organic layer was twice with an aqueous sodium carbonate solution, twice with water, and once with saturated saline.
Washed twice and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and 41.3 g of a crude product of 8-chloro-6-ethoxycarbonyl-5-methylthiochroman-4-one (yield: 85
%).

NMR (ppm, solvent: heavy acetone, internal standard: tetramethylsilane): 1.38 (3H, t), 2.58 (3H, s), 2.9-3.
1 (2H, m), 3.3 to 3.5 (2H, m), 4.34 (2H, q), 7.81
(H, s) Step (6) 88.4 g (311) of 8-chloro-6-ethoxycarbonyl-5-methylthiochroman-4-one obtained in the above step (5).
Mmol) was dissolved in 200 ml of ethanol and further dissolved in 200 ml of dichloromethane. The solution was cooled to 5-10 ° C., and 5.9 g (155 mmol) of sodium borohydride was added thereto. After stirring the reaction solution at the same temperature for 30 minutes,
The mixture was further stirred at room temperature for 3 hours. Then, the reaction solution is
After pouring into 400 ml of aqueous hydrochloric acid and extracting with 900 ml of dichloromethane, the resulting organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off and 8-chloro-6-ethoxycarbonyl-5-methylthiochroman-
86.8 g of 4-ol (97% yield) was obtained.

NMR (ppm, solvent: heavy acetone, internal standard: tetramethylsilane): 1.35 (3H, s), 1.6 to 3.7 (5H, m), 2.6
2 (3H, s), 4.1 to 4.8 (2H, bs), 4.32 (2H, q), 5.13
(H, m), 7.71 (H, s) Step (7) 25.8 g of 8-chloro-6-ethoxycarbonyl-5-methylthiochroman-4-ol obtained in the above step (6) (9
0.0 mmol) was dissolved in 70 ml of acetic acid, 46.0 ml (0.45 mol, 5.0 equivalents) of a 30% aqueous hydrogen peroxide solution was added, and the mixture was heated with stirring at 80 ° C. for 4 hours. The reaction mixture was allowed to cool, and the resulting solid was filtered off, washed with 200 ml of water, dried under reduced pressure, and treated with 8-chloro-6.
21.9 g (95% yield) of -ethoxycarbonyl-4-hydroxy-5-methylthiochroman-1,1-dioxide were obtained.

NMR (ppm, solvent: deuterated chloroform, internal standard: tetramethylsilane): 1.40 (3H, t), 2.59 (3H, s), 2.5
~ 4.2 (4H, m), 4.40 (2H, q), 5.09 (H, bs), 7.67
(H, s) Step (8) 8-chloro-6-ethoxycarbonyl-4-hydroxy-5-methylthiochroman-1, obtained in the step (7),
1-dioxide 10.0 g (31.3 mmol) in ethanol 30 ml
In water, 50% 16% aqueous potassium hydroxide solution and 6.1 g zinc dust
(93.3 mmol, 3.0 equivalents), and the mixture was heated and stirred at 50 ° C. for 3 hours. After completion of the reaction, zinc was filtered. While cooling the reaction solution, a 2N aqueous hydrochloric acid solution was added until the pH reached 1. Thereafter, the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off to give 11.5 g of 4-hydroxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide (yield 100
%).

NMR (ppm, solvent: heavy acetone, internal standard: tetramethylsilane): 2.5 to 2.8 (2H, m), 2.69 (3H, s), 3.1
~ 4.1 (4H, m), 5.22 (H, t), 7.75 (H, d), 7.94 (H,
d) mp.172 ° -173 ° C. Step (9) 3.0 g of 4-hydroxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide obtained in the above step (8) (1
(1.8 mmol) was dissolved in 10 ml of toluene, 0.1 ml of concentrated sulfuric acid was added, and the mixture was heated and stirred at 70 ° C. for 5 hours. After the completion of the reaction, a saturated aqueous solution of sodium hydrogen carbonate was added to the solution with cooling until the pH reached 10. After extracting impurities with ethyl acetate, the aqueous layer was adjusted to pH 1 with 5% hydrochloric acid in an ice bath, and extracted with ethyl acetate.
Extracted times. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off to give 5-methyl-3,4-dehydrothiochroman-6-carboxylic acid-
2.5 g (89% yield) of 1,1-dioxide was obtained.

NMR (ppm, solvent: heavy acetone, internal standard: tetramethylsilane): 2.62 (3H, s), 4.10 (2H, m), 6.45
(H, ddd), 7.20 (H, d), 7.83 (H, d), 7.95 (H, d) mp.183-186 ° C Next, a production example of a novel pyrazole derivative which achieves the first object of the present invention. Is shown.

Production Example 1 In a 100 ml eggplant flask, 3,3,
1.0 g (3.9 mmol) of 4,7-tetramethyl-2-hydrobenzo [b] thiophene-5-carboxylic acid-1,1-dioxide, 0.48 g of 1-ethyl-5-hydroxypyrazole
(4.3 mmol, 1.1 equivalent), t-amyl alcohol 100m
l, 1.04 g (5.0 mmol, 1.3 equivalents) of N, N'-dicyclohexylcarbodiimide (DCC) as a dehydrating agent was added, and the mixture was reacted at room temperature for 4 hours. Add potassium carbonate as a base to the reaction solution.
0.53 g (3.9 mmol, 1 equivalent) was added, and the mixture was further reacted at 100 ° C. for 2 hours. After completion of the reaction, the solvent was distilled off, 50 ml of ethyl acetate and 50 ml of water were added, and the mixture was separated. The resulting aqueous layer was neutralized with 5% hydrochloric acid, extracted with ethyl acetate, the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off. , 4,7-Tetramethyl-5
-(1-ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophene-
0.8 g (57% yield) of 1,1-dioxide (Compound No. 94) was obtained.

Production Example 2 0.76 g (2.8 mmol) of 4,5,8-trimethylthiochroman-6-carboxylic acid-1,1-dioxide, 0.35 g of 1-ethyl-5-hydroxypyrazole in a 50 ml eggplant flask
(3.1 mmol, 1.1 equivalent), 5 ml of t-amyl alcohol
And N, N'-dicyclohexylcarbodiimide (DC
C) A solution of 0.70 g (3.4 mmol, 1.2 equivalents) in 5 ml of t-amyl alcohol was added at room temperature. After reacting at room temperature for 2 hours, 0.58 g (2.8 mmol, 1.5 equivalents) of potassium carbonate was added, and the mixture was reacted at 100 ° C. for 6 hours. After the solvent was distilled off, the residue was partitioned between water (30 ml) and ethyl acetate (30 ml).
The urea body was separated by filtration. Organic layer is 5% potassium carbonate aqueous solution
After extracting twice with 10 ml, the aqueous layers were combined, acidified with concentrated hydrochloric acid, and extracted with ethyl acetate. After washing with saturated saline,
Dry over sodium sulfate and evaporate the solvent to give
77 g was obtained. This was recrystallized from ethanol to give 0.52 g (yield) of 4,5,8-trimethyl-6- (1-ethyl-5-hydroxypyrazol-4-yl) carbonylthiochroman-1,1-dioxide (compound No. 302). 51%).

Preparation Example 3 Preparation of Intermediate Example 3 in 5 ml of tert-amyl alcohol
4-ethyl-5,8-dimethylthiochroman-6 obtained in
0.90 g (3.2 mmol) of carboxylic acid-1,1-dioxide,
0.43 g (3.8 mmol) of 1-ethyl-5-hydroxypyrazole and 0.79 (3.8 mmol) of DCC were added, and the mixture was added at room temperature for 2 hours.
The reaction was performed for 5 hours. Subsequently, 0.31 g (2.2 mmol) of potassium carbonate was added and reacted at 80 ° C. for 4 hours. The reaction mixture was cooled to room temperature, and the solvent was distilled off under reduced pressure. 2% for residue
An aqueous solution of sodium carbonate was added to dissolve, and insolubles were removed by filtration. After washing the aqueous solution with ethyl acetate, 12N hydrochloric acid was added to adjust the pH to 1, and the resulting oil was extracted with ethyl acetate. The ethyl acetate layer was separated, washed with saturated saline, and the solvent was distilled off under reduced pressure to give 4-ethyl-5,8-dimethyl-6.
1.2 g (100% yield) of-(1-ethyl-5-hydroxypyrazol-4-yl) carbonylthiochroman-1,1-dioxide (Compound No. 301) was obtained.

Production Example 4 2.38 g (9.4 mmol) of 3,4,7-trimethyl-2-hydrobenzo [b] thiophen-5-carboxylic acid-1,1-dioxide in a 50 ml eggplant flask, 1-ethyl-5-hydroxypyrazole 1.15 g (10.3 mmol, 1.1 equivalent), t
10 ml of amyl alcohol were charged and a solution of 2.31 g (12.2 mmol, 1.3 equivalents) of DCC in 5 ml of t-amyl alcohol was added at room temperature. After reacting for 2 hours at room temperature, potassium carbonate 1.
68 g (12.2 mmol, 3 equivalents) was added and reacted at 100 ° C. for 6 hours. After evaporating the solvent, the residue was partitioned between water (50 ml) and ethyl acetate (50 ml), and the insoluble DCC urea compound was separated by filtration. After the organic layer was extracted twice with 15 ml of a 5% aqueous potassium carbonate solution, the aqueous layers were combined, acidified with concentrated hydrochloric acid, and extracted with ethyl acetate. After washing with saturated saline, drying over sodium sulfate and distilling off the solvent, 2.34 g of a crude product of the desired product was obtained. This was recrystallized from ethanol to give 3,4,7-trimethyl-5.
-(1-ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophene-
1.39 g (yield 42%) of 1,1-dioxide (Compound No. 82) was obtained.

Production Example 5 Step (1) Obtained in the above Intermediate Production Example 5 in a 100 ml eggplant flask.
0.98 g (4.4 mmol) of 5,8-dimethyl-3,4-dehydrothiochroman-6-carboxylic acid, 0.54 g (4.8 mmol, 1.1 equivalent) of 1-ethyl-5-hydroxypyrazole and 10 ml of dichloromethane were added, and a dehydrating agent was added. Was added and reacted at room temperature for 2 hours. DCC
After removing the urea body by filtration and concentrating the filtrate, purification was performed by silica gel column chromatography (developing solvent: ethyl acetate, n-hexane, 1: 1 mixed solvent). To 0.81 g (2.6 mmol) of the purified ester intermediate, 0.53 g (3.9 mmol, 1.5 equivalents) of potassium carbonate as a base and 2.0 ml of 1,4-dioxane were added, and the mixture was further reacted at 120 ° C. for 2 hours. After completion of the reaction, the solvent was distilled off, and the residue was diluted with 50 ml of ethyl acetate.
And 50 ml of water were added for liquid separation. The obtained aqueous layer was neutralized with a 5% acid salt, and then extracted with ethyl acetate. The obtained organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off to give 5,8-dimethyl-6- (1-ethyl-5-hydroxypyrazol-4-yl) carbonyl-. 0.63 g of 3,4-dehydrothiochroman (Compound No. 289)
(57% yield).

Step (2) The 5,8-dimethyl-6- (1-ethyl-5-hydroxypyrazole) obtained in the above step (1) is placed in a 30 ml eggplant flask.
4-yl) carbonyl-3,4-dehydrothiochroman 75m
g (0.24 mmol), 7 mg of platinum oxide, and 3 ml of ethanol were added, and hydrogenation was performed at normal pressure at room temperature. After reacting for 8 hours, platinum oxide was removed by filtration, and ethanol was distilled off to give 5,8-dimethyl-.
67 mg (88% yield) of 6- (1-ethyl-5-hydroxypyrazol-4-yl) carbonylthiochroman (Compound No. 290) was obtained. The yield through steps (1) and (2) is
50%.

Preparative Example 6 Instead of 5,8-dimethyl-3,4-dehydrothiochroman-6-carboxylic acid in Preparative Example 5, 5-methyl-3,4-dehydro obtained in Intermediate Preparative Example 10 Except that thiochroman-6-carboxylic acid-1,1-dioxide was used, essentially the same operation as in Preparation Example 5 was carried out to give 5-methyl-6- (1-ethyl-5-hydroxypyrazole-
4-yl) carbonylthiochroman-1,1-dioxide (compound No303) was obtained.

Production Example 7 The 3,3,4,7 obtained in the above Production Example 1 were placed in a 100 ml eggplant flask.
-Tetramethyl-5- (1-ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophene-1,1-dioxide (compound No 94) 0.4
g (1.1 mmol), 10 ml of dichloromethane, 10 ml of water and 0.2 g (1.4 mmol, 1.3 equivalents) of potassium carbonate were added, and 0.19 g (1.3 mmol, 1.2 equivalents) of n-propanesulfonyl chloride was added dropwise at room temperature. After adding 50 mg of benzyltriethylammonium chloride (BTEAC) and reacting at the same temperature for 2 hours, the layers were separated. The obtained aqueous layer was extracted with dichloromethane, and the obtained organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 3,3,4,7.
-Tetramethyl-5- (1-ethyl-5-n-propanesulfonyloxypyrazol-4-yl) carbonyl-
0.45 g (87% yield) of 2-hydrobenzo [b] thiophene-1,1-dioxide (Compound No. 95) was obtained.

Production Example 8 The 3,3,4,7 obtained in the above Production Example 1 was placed in a 100 ml eggplant flask.
-Tetramethyl-5- (1-ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophene-1,1-dioxide 0.4 g (1.1 mmol), dichloromethane 10 ml, water 10 ml, potassium carbonate 0.2g
(1.4 mmol, 1.3 equivalents), and 0.25 g (1.3 mmol, 1.2 equivalents) of p-toluenesulfonyl chloride was added dropwise at room temperature. To this was added 50 mg of benzyltriethylammonium chloride (BTEAC), and the mixture was reacted at the same temperature for 2 hours. The obtained aqueous layer was extracted with dichloromethane, and the obtained organic layer was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 3,3,4,7-
Tetramethyl-5- (1-ethyl-5-p-toluenesulfonyloxypyrazol-4-yl) carbonyl-2
-Hydrobenzo [b] thiophene-5-carboxylic acid-1,
0.52 g (yield 91%) of 1-dioxide (Compound No. 96) was obtained.

Production Example 9 4,5,8-Trimethyl-6- (1
-Ethyl-5-hydroxypyrazol-4-yl) carbonylthiochroman-1,1-dioxide 0.25 g (0.69 mmol), dichloromethane 5 ml, water 5 ml, potassium carbonate 0.09
g (0.69 mmol, 1 equivalent) was added, and 0.11 g (0.76 mmol, 1.1 equivalent) of n-propanesulfonyl chloride was added dropwise with stirring at room temperature. After adding 5 mg of benzyltoluethylammonium chloride (BTEAC) and reacting at the same temperature for 2 hours, the layers were separated and the aqueous layer was extracted with dichloromethane.
The organic layer was washed with saturated saline and dried over sodium sulfate. The solvent was distilled off to obtain 0.35 g of a crude product, which was recrystallized from ethanol to give 4,5,8-trimethyl-6- (1-ethyl-5-n-propanesulfonyloxypyrazole-
0.31 g (yield 95%) of 4-yl) carbonylthiochroman-1,1-dioxide (Compound No. 304) was obtained.

Production Example 10 4,5,8-Trimethyl-6- (1
-Ethyl-5-hydroxypyrazol-4-yl) carbonylthiochroman-1,1-dioxide 0.18 g (0.50 mmol), dichloromethane 5 ml, water 5 ml, potassium carbonate 0.07
g (0.50 mmol, 1 equivalent) was added, and a solution of 0.10 g (0.55 mmol, 1.1 equivalent) of p-toluenesulfonyl chloride in 1 ml of dichloromethane was added dropwise at room temperature while stirring at room temperature. Benzyltriethylammonium chloride (BTEA
C) After adding 5 mg and reacting at the same temperature for 2 hours, liquid separation was performed.
The aqueous layer was extracted with dichloromethane. The organic layer was washed with saturated saline and dried over sodium sulfate. The solvent was distilled off to obtain 0.30 g of a crude product, which was recrystallized from ethanol.
4,5,8-Trimethyl-6- (1-ethyl-5-p-toluenesulfonyloxypyrazol-4-yl) carbonylthiochroman-1,1-dioxide (Compound No. 305)
20 g (yield 77%) was obtained.

Production Example 11 3,4,7-Trimethyl-5- (1
-Ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophen-1,1-dioxide 0.30 g (0.86 mmol), dichloromethane 5 ml,
5 ml of water, 0.12 g of potassium carbonate (0.69 mmol, 0.8 equivalent)
And 0.16 g (0.95 mmol, 1.1 equivalent) of n-propanesulfonyl chloride was added dropwise with stirring at room temperature. After adding 5 mg of benzyltriethylammonium chloride (BTEAC) and reacting at the same temperature for 2 hours, the layers were separated and the aqueous layer was extracted with dichloromethane. The organic layer was washed with saturated saline and dried over sodium sulfate. The solvent was distilled off to obtain 0.40 g of a crude product, which was recrystallized from ethanol to give 3,4,7-trimethyl-5- (1-ethyl-5-n-propanesulfonyloxypyrazol-4-yl)-. 0.31 g (79% yield) of 2-hydrobenzo [b] thiophenecarbonyl-1,1-dioxide (compound No83) was obtained.

Production Example 12 3,4,7-Trimethyl-5- (1
-Ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophene-1,1-dioxide in 0.25 g (0.72 mmol) in dichloromethane 5m
l, 5 ml of water and 0.10 g (0.72 mmol, 1 equivalent) of potassium carbonate were added, and a solution of 0.15 g (0.72 mmol, 1.1 equivalent) of p-toluenesulfonyl chloride in 1 ml of dichloromethane was added dropwise at room temperature while stirring at room temperature. After adding 5 mg of benzyltriethylammonium chloride (BTEAC) and reacting at the same temperature for 2 hours, the layers were separated and the aqueous layer was extracted with dichloromethane. The organic layer was washed with saturated saline and dried over sodium sulfate. The solvent was distilled off to obtain 0.34 g of a crude product, which was recrystallized from ethanol to give 3,4,7-trimethyl-5- (1
-Ethyl-p-toluenesulfonyloxypyrazole-
0.29 g (yield 80) of 4-yl) carbonyl-2-hydrobenzo [b] thiophene-1,1-dioxide (Compound No. 84)
%)Obtained.

Production Example 13 3,4,7-Trimethyl-5- (1
-Ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophen-1,1-dioxide 0.30 g (0.86 mmol), dichloromethane 5 ml,
5 ml of water, 0.12 g of potassium carbonate (0.69 mmol, 0.8 equivalent)
Ethanesulfonyl chloride while stirring at room temperature
0.12 g (0.95 mmol, 1.1 eq) was added dropwise. After adding 5 mg of benzyltriethylammonium chloride (BTEAC) and reacting at the same temperature for 2 hours, the layers were separated and the aqueous layer was extracted with dichloromethane. After washing the organic layer with saturated saline,
Dried over sodium sulfate. The solvent was distilled off to obtain crude product 0.
35 g was obtained and recrystallized from ethanol to give 3,4,7-trimethyl-5- (1-ethyl-ethanesulfonyloxypyrazol-4-yl) -2-hydrobenzo [b] thiophenecarbonyl-1,1-dioxide 0.24 g of (Compound No306)
(63% yield).

Production Example 14 3,4,7-Trimethyl-5- (1
-Ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophen-1,1-dioxide 0.30 g (0.86 mmol), dichloromethane 5 ml,
Pyridine 0.09 g (1.1 mmol, 1.3 equivalents) was added, and 0.10 g (0.95 mmol, 1.1 equivalents) of isobutyric acid chloride was added dropwise with stirring under ice cooling. After stirring for 30 minutes under ice cooling,
The reaction was performed at room temperature for 2 hours. After adding 5 ml of water to stop the reaction, the aqueous layer was extracted with dichloromethane. 5 organic layers
The extract was washed with 5% hydrochloric acid, 5% potassium carbonate, and then with saturated saline, and then dried over sodium sulfate. The solvent was distilled off to obtain 0.28 g of a crude product, which was recrystallized from ethanol to give 3,4,7-trimethyl-5- (1-ethyl-5-isopropylcarbonyloxypyrazol-4-yl) -2-hydrobenzo. [B] 0.27 g (yield 75%) of thiophenecarbonyl-1,1-dioxide (compound No. 307) was obtained.

Production Example 15 3,4,7-Trimethyl-5- (1
-Ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophen-1,1-dioxide 0.24 g (0.69 mmol), dichloromethane 5 ml,
Pyridine 0.07 g (0.89 mmol, 1.3 equivalent) was added, and cyclohexanecarboxylic acid chloride 0.11 was added with stirring under ice cooling.
g (0.76 mmol, 1.1 eq) was added dropwise. After stirring for 30 minutes under ice-cooling, the mixture was reacted at room temperature for 2 hours. After adding 5 ml of water to stop the reaction, the aqueous layer was extracted with dichloromethane. The organic layer was washed with 5% hydrochloric acid, 5% potassium carbonate, and then with saturated saline, and then dried over sodium sulfate. The solvent was distilled off to obtain 0.35 g of a crude product, which was recrystallized from ethanol to give 3,4,7-trimethyl-5- (1-ethyl-5-carbonyloxypyrazol-4-yl) -2-hydrobenzo [ b] 0.32 g (100% yield) of thiophenecarbonyl-1,1-dioxide (Compound No. 308) was obtained.

Production Example 16 0.30 g (0.86 mmol) of 5-methyl-6- (1-ethyl-5-hydroxypyrazol-4-yl) carbonylthiochroman-1,1-dioxide in a 30 ml eggplant flask,
25 ml of dichloromethane, 5 ml of water, 0.14 g of potassium carbonate (0.86
Mmol, 1 equivalent) and 0.14 g (0.95 mmol, 1.1 equivalent) of n-propanesulfonyl chloride was added dropwise with stirring at room temperature. After adding 5 mg of benzyltriethylammonium chloride (BTEAC) and reacting at the same temperature for 2 hours, the layers were separated and the aqueous layer was extracted with dichloromethane. The organic layer was washed with saturated saline and dried over sodium sulfate. The solvent was distilled off to obtain 0.21 g of a crude product, which was recrystallized from ethanol to give 5-methyl-6- (1-ethyl-5-n-
Propanesulfonyloxypyrazol-4-yl) carbonylthiochroman-1,1-dioxide (Compound No309)
0.18 g (yield 48%) was obtained.

Production Example 17 0.26 g (0.75 mmol) of 5-methyl-6- (1-ethyl-5-hydroxypyrazol-4-yl) carbonylthiochroman-1,1-dioxide in a 30 ml eggplant flask
Into, dichloromethane 5ml, water 5ml, potassium carbonate 0.10g
(0.72 mmol, 1 equivalent) was added, and while stirring at room temperature, a solution of 0.16 g (0.82 mmol, 1.1 equivalent) of p-toluenesulfonyl chloride in 1 ml of dichloromethane was added dropwise at room temperature. Benzyltriethylammonium chloride (BTEA
C) After adding 5 mg and reacting at the same temperature for 2 hours, liquid separation was performed.
The aqueous layer was extracted with dichloromethane. The organic layer was washed with saturated saline and dried over sodium sulfate. The solvent was distilled off to obtain 0.24 g of a crude product.
0.14 g of -methyl-6- (1-ethyl-p-toluenesulfonyloxypyrazol-4-yl) carbonylthiochroman-1,1-dioxide (compound No. 310) (yield: 92)
%)Obtained.

Production Example 18 The 3,4,7-trimethyl-5- (1
Instead of -ethyl-5-hydroxypyrazol-4-yl) carbonyl-2-hydrobenzo [b] thiophen-1,1-dioxide, 5-methyl-6- (1-ethyl- 5-hydroxypyrazole-4
-Yl) carbonylthiochroman-1,1-dioxide, but essentially the same procedure as in Preparation Example 15 was carried out to give 5-methyl-6- (1-ethyl-5-cyclohexylcarbonyloxypyrazole-4). -Yl) carbonylthiochroman-1,1-dioxide (Compound No. 311) was obtained.

Table 2 shows the structural formulas and yields of the starting materials or reaction reagents used in Production Examples 1 to 18 and the obtained compounds, and Table 3 shows the physical properties.

Next, examples of herbicides that achieve the second object of the present invention will be described.

Examples of herbicides and comparative examples of herbicides (1) Preparation of herbicide 97 parts by weight of talc (trade name: Sigleite, manufactured by Sigleite Industry Co., Ltd.) as a carrier, and alkylaryl sulfonate (trade name) as a surfactant Name: Neoperex,
1.5 parts by weight of Kao Atlas Co., Ltd.) and nonionic and anionic surfactants (trade name: Solpol 800A,
1.5 parts by weight of Toho Chemical Industry Co., Ltd.) were uniformly pulverized and mixed to obtain a wettable powder carrier.

90 parts by weight of this carrier for wettable powders and 10 parts by weight of each of the compounds of the present invention obtained in the above Production Examples were uniformly ground and mixed to obtain herbicides. Herbicide Comparative Examples 1 and 3 were similarly prepared using the following compound (x), and Herbicide Comparative Examples 2, 4 and 6 were prepared in the same manner using 10 parts by weight of the following compound (y).

Compound (x): Commercial herbicide pyrazolate Compound (y): Compound described in JP-A-63-122672. (2) Biological test (foliage treatment test, herbicides Examples 1 to 5 and Comparative Examples 1 and 2) Weed seeds of Meishiba, Nobie, Enokorogosa, Onamimi, Ichibai and Aoubiyu in 1/5000 are Wagner pot filled with field soil And seeds of corn, wheat and barley, covered with soil and grown in a greenhouse.
In the second to second leaf stages, a predetermined amount of the herbicide obtained in the above (1) was suspended in water and sprayed uniformly onto the foliage at a liquid volume of 200 liters / 10 ares. Thereafter, the plants were grown in a greenhouse, and the herbicidal effect was determined 20 days after the spraying treatment. Table 4 shows the results.

The herbicidal effect and crop damage were indicated according to the following criteria.

Here, the unprocessed ratio of the residual grass weight = (the residual grass weight of the treated plot / the residual grass weight of the untreated plot) × 100. The same applies to the following biological tests.

(Criteria) Herbicidal effect No treatment ratio of residual weight of herb (%) 0 81-100 1 61-80 2 41-60 3 21-40 40 1-20 5 0 Damage to crops No treatment ratio of residual herb weight (%)-100 ± 95-99 + 90-94 ++ 80-89 ++ 0-79 (3) Biological test (field soil treatment test, herbicide Examples 6 to
10 and herbicides Comparative Examples 3 and 4) Weed seeds of corngrass, Nobie, Enokorogusa, Onamimomi, Ichibai, Aoubiyu and corn, wheat, barley seeds were seeded in a 1/5000 are Wagner pot filled with field soil, and after soil covering. A predetermined amount of the herbicide obtained in the above (1) was suspended in water and uniformly dispersed on the soil surface. Thereafter, the plants were grown in a greenhouse, and the herbicidal effect was determined 20 days after the spraying treatment. Table 5 shows the results.

The herbicidal effect and crop damage were indicated in accordance with the criteria described in (2) Foliage treatment test.

(4) Biological test (field soil treatment test, herbicide Examples 11 to
21 and Comparative Example 5) Weed seeds of corngrass, Nobie, Enokorogusa, Onamomi, Ichibai, Aoubiyu and corn were sown in a 1/5000 are Wagner pot filled with field soil, and after covering the soil, the predetermined amount obtained in (1) above Suspended herbicide in water,
Spread evenly on the soil surface. After that, grow in the greenhouse,
Twenty days after the spraying treatment, the herbicidal effect and the phytotoxicity of corn were determined. Table 6 shows the results.

The herbicidal effect and crop damage were indicated in accordance with the criteria described in (2) Foliage treatment test.

As described above in detail, according to the present invention, corn, wheat, barley and other useful crops do not cause phytotoxicity, both grass treatment and broadleaf weed foliage treatment, in any treatment of soil treatment A novel pyrazole derivative which can be selectively controlled at a low dose and a herbicide containing the above-mentioned novel pyrazole derivative as an active ingredient are provided.

──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Kazuyoshi Koike 1280 Kamiizumi, Sodegaura-shi, Chiba Idemitsu Kosan Co., Ltd. (58) Field surveyed (Int. Cl. ⁷ , DB name) C07D 409/06 A01N 43 / 56 CA (STN) CAOLD (STN) REGISTRY (STN)

Claims (18)

(57) [Claims] 1. The compound of the formula (IA) Wherein R ¹ is a hydrogen atom or a C ₁ -C ₄ alkyl group; R ² is a C ₁ -C ₄ alkyl group; Z ¹ and Z ² are each independently a hydrogen atom, a halogen atom and is one kind selected from the group consisting of C ₁ -C ₄ alkyl group; X ¹ and X ⁴ are, one selected from each independently a hydrogen atom, the group consisting of halogen atom and C ₁ -C ₄ alkyl group X ⁵ and X ⁶ are each independently a hydrogen atom or C ₁ -C ₄
Q is a hydrogen atom or a group represented by the formula -AB, wherein Z is an alkyl group, or Z ¹ and X ⁵ can be bonded to each other to form an unsaturated bond; ₂ - group, one selected from the group consisting of -CO- group and -CH ₂ CO- group, B is C ₁ -C ₈ alkyl group, C ₃ -C ₈ cycloalkyl group and the formula (V) Wherein Y is one selected from the group consisting of a halogen atom, a nitro group, a C ₁ -C ₄ alkyl group, a C ₁ -C ₄ alkoxy group and a C ₁ -C ₄ haloalkyl group; 1 or 2
Represents an integer. ) Is selected from the group consisting of:
And n represents 0, 1 or 2. A pyrazole derivative represented by｝ or a salt thereof. 2. The pyrazole derivative of the formula (IA) according to claim 1, wherein Z ¹ is a C ₁ -C ₄ alkyl group, and Z ² is a hydrogen atom or a C ₁ -C ₄ alkyl group. salt. 3. The pyrazole derivative of the formula (IA) or a salt thereof according to claim 1, wherein X ¹ and X ⁴ are each independently a C ₁ -C ₄ alkyl group. 4. The formula (IB) Wherein R ¹ is a hydrogen atom or a C ₁ -C ₄ alkyl group; R ² is a C ₁ -C ₄ alkyl group; and Z ² is a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group. X ¹ and X ⁴ are each independently selected from the group consisting of a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group; X ⁶ , X ⁷ And X ⁸ are each independently a hydrogen atom or C ₁
Be -C ₄ alkyl group; Q is the radical [formula represented by hydrogen or the formula -A-B, A is -SO ₂ - from the group consisting of group, -CO- group and -CH ₂ CO- group B is a C ₁ -C ₈ alkyl group, a C ₃ -C ₈ cycloalkyl group and the formula (V) Wherein Y is one selected from the group consisting of a halogen atom, a nitro group, a C ₁ -C ₄ alkyl group, a C ₁ -C ₄ alkoxy group and a C ₁ -C ₄ haloalkyl group; 1 or 2
Represents an integer. ) Is selected from the group consisting of:
And n represents 0, 1 or 2. A pyrazole derivative represented by｝ or a salt thereof. 5. The compound of claim 4, wherein n is 0.
A pyrazole derivative of B) or a salt thereof. 6. The pyrazole derivative of the formula (IB) or a salt thereof according to claim 4, wherein X ¹ and X ⁴ are each independently a C ₁ -C ₄ alkyl group. 7. A compound of the formula (IC) Wherein R ¹ is a hydrogen atom or a C ₁ -C ₄ alkyl group; R ² is a C ₁ -C ₄ alkyl group; X ¹ and X ⁴ are each independently a hydrogen atom, a halogen atom and is one kind selected from the group consisting of C ₁ -C ₄ alkyl ^{group; X 5, X 6, X} 7 and X ⁸ are either each independently a hydrogen atom or a C ₁ -C ₄ alkyl group, or X ⁵ and X ⁷ can combine with each other to form an unsaturated bond; Q is a hydrogen atom or a group represented by the formula -AB, wherein A is a -SO ₂ -group, -CO- is one kind selected from the group consisting of radicals and -CH ₂ CO- group, B is C ₁ -C ₈ alkyl group, C ₃ -C ₈ cycloalkyl group and the formula (V) Wherein Y is one selected from the group consisting of a halogen atom, a nitro group, a C ₁ -C ₄ alkyl group, a C ₁ -C ₄ alkoxy group and a C ₁ -C ₄ haloalkyl group; 1 or 2
Represents an integer. ) Is selected from the group consisting of:
And n represents 0, 1 or 2. A pyrazole derivative represented by｝ or a salt thereof. 8. The pyrazole derivative of the formula (IC) or a pyrazole derivative thereof according to claim 7, wherein X ¹ is a C ₁ -C 4 alkyl group, and X ⁴ is a hydrogen atom or a C ₁ -C ₄ alkyl group. salt. 9. The pyrazole derivative of the formula (IC) or a salt thereof according to claim 7, wherein n is 0 or 2. 10. The formula (ID) Wherein R ¹ is a hydrogen atom or a C ₁ -C ₄ alkyl group; R ² is a C ₁ -C ₄ alkyl group; Z ³ is a halogen atom or a C ₁ -C ₄ alkyl group; ¹ and X ⁴ are each independently one selected from the group consisting of a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group; X ⁵ , X ⁶ , X ⁷ and X ⁸ are each independently Is a hydrogen atom or a C ₁ -C ₄ alkyl group, or X ⁵ and X ⁷ can be bonded to each other to form an unsaturated bond; Q is a hydrogen atom or represented by the formula —AB A group wherein A is one selected from the group consisting of a —SO ₂ — group, a —CO— group and a —CH ₂ CO— group, and B is a C ₁ -C ₈ alkyl group, C ₃ -C ₈ Cycloalkyl group and formula (V) Wherein Y is one selected from the group consisting of a halogen atom, a nitro group, a C ₁ -C ₄ alkyl group, a C ₁ -C ₄ alkoxy group and a C ₁ -C ₄ haloalkyl group; 1 or 2
Represents an integer. ) Is selected from the group consisting of:
And n represents 0, 1 or 2. A pyrazole derivative represented by｝ or a salt thereof. 11. X ¹ and X ⁴ each independently represent C ₁ -C ₄
11. The pyrazole derivative of the formula (ID) or a salt thereof according to claim 10, which is an alkyl group. 12. The method according to claim 10, wherein Z ³ is a C ₁ -C ₄ alkyl group.
Or a salt thereof. 13. The pyrazole derivative of the formula (ID) or a salt thereof according to claim 12, wherein Z ³ is a methyl group or an ethyl group. 14. A herbicide comprising the pyrazole derivative and / or a salt thereof according to claim 1 as an active ingredient. 15. A compound of the formula (II-A) X ¹ and X ⁴ are each independently a halogen atom or C ₁
Be -C ₄ alkyl group; Z ¹ and Z ² are one selected from each independently a hydrogen atom, the group consisting of halogen atom and C ₁ -C ₄ alkyl group; X ⁵ and X ^6, Each independently a hydrogen atom or C ₁ -C ₄
Is an alkyl group, or Z ¹ and X ⁵ can be bonded to each other to form an unsaturated bond; n represents 0, 1 or 2; An aromatic carboxylic acid derivative represented by｝ or a salt thereof. 16. The formula (II-B) Wherein Z ² is one selected from the group consisting of a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group; X ¹ and X ⁴ are each independently a hydrogen atom, a halogen atom and C ₁ is one kind selected from the group consisting of -C ₄ alkyl group; X ^6, X ⁷ and X ⁸ is a hydrogen atom or a C ₁ independently
It is -C ₄ alkyl group; n represents 0, 1 or 2. An aromatic carboxylic acid derivative represented by｝ or a salt thereof. 17. Formula (II-C) Wherein X ¹ and X ⁴ are each independently one selected from the group consisting of a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group; X ⁵ , X ⁶ , X ⁷ and X ⁸ Are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group, or X ⁵ and X ⁷ can combine with each other to form an unsaturated bond; n represents 0, 1 or 2 . An aromatic carboxylic acid derivative represented by｝ or a salt thereof. 18. Formula (II-D) Wherein Z ³ is a halogen atom and a C ₁ -C ₄ alkyl group; X ¹ and X ⁴ are each independently selected from the group consisting of a hydrogen atom, a halogen atom and a C ₁ -C ₄ alkyl group X ⁵ , X ⁶ , X ⁷ and X ⁸ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group, or X ⁵ and X ⁷ are bonded to each other to form an unsaturated bond And n represents 0, 1 or 2. An aromatic carboxylic acid derivative represented by｝ or a salt thereof.